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Sample records for membrane biophysics

  1. Role of Membrane Biophysics in Alzheimer's - related cell pathways

    Directory of Open Access Journals (Sweden)

    Donghui eZhu

    2015-05-01

    Full Text Available Cellular membrane alterations are commonly observed in many diseases, including Alzheimer’s disease (AD. Membrane biophysical properties, such as membrane molecular order, membrane fluidity, organization of lipid rafts, and adhesion between membrane and cytoskeleton, play an important role in various cellular activities and functions. While membrane biophysics impacts a broad range of cellular pathways, this review addresses the role of membrane biophysics in amyloid-β peptide aggregation, Aβ-induced oxidative pathways, amyloid precursor protein processing, and cerebral endothelial functions in AD. Understanding the mechanism(s underlying the effects of cell membrane properties on cellular processes should shed light on the development of new preventive and therapeutic strategies for this devastating disease.

  2. Biophysical EPR Studies Applied to Membrane Proteins

    Science.gov (United States)

    Sahu, Indra D; Lorigan, Gary A

    2015-01-01

    Membrane proteins are very important in controlling bioenergetics, functional activity, and initializing signal pathways in a wide variety of complicated biological systems. They also represent approximately 50% of the potential drug targets. EPR spectroscopy is a very popular and powerful biophysical tool that is used to study the structural and dynamic properties of membrane proteins. In this article, a basic overview of the most commonly used EPR techniques and examples of recent applications to answer pertinent structural and dynamic related questions on membrane protein systems will be presented. PMID:26855825

  3. Plasma membrane--cortical cytoskeleton interactions: a cell biology approach with biophysical considerations.

    Science.gov (United States)

    Kapus, András; Janmey, Paul

    2013-07-01

    From a biophysical standpoint, the interface between the cell membrane and the cytoskeleton is an intriguing site where a "two-dimensional fluid" interacts with an exceedingly complex three-dimensional protein meshwork. The membrane is a key regulator of the cytoskeleton, which not only provides docking sites for cytoskeletal elements through transmembrane proteins, lipid binding-based, and electrostatic interactions, but also serves as the source of the signaling events and molecules that control cytoskeletal organization and remolding. Conversely, the cytoskeleton is a key determinant of the biophysical and biochemical properties of the membrane, including its shape, tension, movement, composition, as well as the mobility, partitioning, and recycling of its constituents. From a cell biological standpoint, the membrane-cytoskeleton interplay underlies--as a central executor and/or regulator--a multitude of complex processes including chemical and mechanical signal transduction, motility/migration, endo-/exo-/phagocytosis, and other forms of membrane traffic, cell-cell, and cell-matrix adhesion. The aim of this article is to provide an overview of the tight structural and functional coupling between the membrane and the cytoskeleton. As biophysical approaches, both theoretical and experimental, proved to be instrumental for our understanding of the membrane/cytoskeleton interplay, this review will "oscillate" between the cell biological phenomena and the corresponding biophysical principles and considerations. After describing the types of connections between the membrane and the cytoskeleton, we will focus on a few key physical parameters and processes (force generation, curvature, tension, and surface charge) and will discuss how these contribute to a variety of fundamental cell biological functions. © 2013 American Physiological Society.

  4. Biophysics conference 1978

    International Nuclear Information System (INIS)

    1978-01-01

    The main subject on the biophysics meeting was the biophysics of membranes with practical subjects from photosynthesis and the transfer processes on membranes. In radiation biophysics, problems of radiation sensitisation, immunological problems after radiation exposure, the oxygen effect and inhibitory processes in RNS synthesis after radiation exposure were discussed with a view to tumour therapy. (AJ) [de

  5. Biophysical properties of membrane lipids of anammox bacteria : I. Ladderane phospholipids form highly organized fluid membranes

    NARCIS (Netherlands)

    Boumann, Henry A.; Longo, Marjorie L.; Stroeve, Pieter; Poolman, Bert; Hopmans, Ellen C.; Stuart, Marc C. A.; Damste, Jaap S. Sinninghe; Schouten, Stefan

    Anammox bacteria that are capable of anaerobically oxidizing ammonium (anammox) with nitrite to nitrogen gas produce unique membrane phospholipids that comprise hydrocarbon chains with three or five linearly condensed cyclobutane rings. To gain insight into the biophysical properties of these

  6. Exploring the biophysical properties of phytosterols in the plasma membrane for novel cancer prevention strategies.

    Science.gov (United States)

    Fakih, Omar; Sanver, Didem; Kane, David; Thorne, James L

    2018-05-03

    Cancer is a global problem with no sign that incidences are reducing. The great costs associated with curing cancer, through developing novel treatments and applying patented therapies, is an increasing burden to developed and developing nations alike. These financial and societal problems will be alleviated by research efforts into prevention, or treatments that utilise off-patent or repurposed agents. Phytosterols are natural components of the diet found in an array of seeds, nuts and vegetables and have been added to several consumer food products for the management of cardio-vascular disease through their ability to lower LDL-cholesterol levels. In this review, we provide a connected view between the fields of structural biophysics and cellular and molecular biology to evaluate the growing evidence that phytosterols impair oncogenic pathways in a range of cancer types. The current state of understanding of how phytosterols alter the biophysical properties of plasma membrane is described, and the potential for phytosterols to be repurposed from cardio-vascular to oncology therapeutics. Through an overview of the types of biophysical and molecular biology experiments that have been performed to date, this review informs the reader of the molecular and biophysical mechanisms through which phytosterols could have anti-cancer properties via their interactions with the plasma cell membrane. We also outline emerging and under-explored areas such as computational modelling, improved biomimetic membranes and ex vivo tissue evaluation. Focus of future research in these areas should improve understanding, not just of phytosterols in cancer cell biology but also to give insights into the interaction between the plasma membrane and the genome. These fields are increasingly providing meaningful biological and clinical data but iterative experiments between molecular biology assays, biosynthetic membrane studies and computational membrane modelling improve and refine our

  7. Interplay of mycolic acids, antimycobacterial compounds and pulmonary surfactant membrane: a biophysical approach to disease.

    Science.gov (United States)

    Pinheiro, Marina; Giner-Casares, Juan J; Lúcio, Marlene; Caio, João M; Moiteiro, Cristina; Lima, José L F C; Reis, Salette; Camacho, Luis

    2013-02-01

    This work focuses on the interaction of mycolic acids (MAs) and two antimycobacterial compounds (Rifabutin and N'-acetyl-Rifabutin) at the pulmonary membrane level to convey a biophysical perspective of their role in disease. For this purpose, accurate biophysical techniques (Langmuir isotherms, Brewster angle microscopy, and polarization-modulation infrared reflection spectroscopy) and lipid model systems were used to mimic biomembranes: MAs mimic bacterial lipids of the Mycobacterium tuberculosis (MTb) membrane, whereas Curosurf® was used as the human pulmonary surfactant (PS) membrane model. The results obtained show that high quantities of MAs are responsible for significant changes on PS biophysical properties. At the dynamic inspiratory surface tension, high amounts of MAs decrease the order of the lipid monolayer, which appears to be a concentration dependent effect. These results suggest that the amount of MAs might play a critical role in the initial access of the bacteria to their targets. Both molecules also interact with the PS monolayer at the dynamic inspiratory surface. However, in the presence of higher amounts of MAs, both compounds improve the phospholipid packing and, therefore, the order of the lipid surfactant monolayer. In summary, this work discloses the putative protective effects of antimycobacterial compounds against the MAs induced biophysical impairment of PS lipid monolayers. These protective effects are most of the times overlooked, but can constitute an additional therapeutic value in the treatment of pulmonary tuberculosis (Tb) and may provide significant insights for the design of new and more efficient anti-Tb drugs based on their behavior as membrane ordering agents. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Membrane Biophysics

    CERN Document Server

    Ashrafuzzaman, Mohammad

    2013-01-01

    Physics, mathematics and chemistry all play a vital role in understanding the true nature and functioning of biological membranes, key elements of living processes. Besides simple spectroscopic observations and electrical measurements of membranes we address in this book the phenomena of coexistence and independent existence of different membrane components using various theoretical approaches. This treatment will be helpful for readers who want to understand biological processes by applying both simple observations and fundamental scientific analysis. It provides a deep understanding of the causes and effects of processes inside membranes, and will thus eventually open new doors for high-level pharmaceutical approaches towards fighting membrane- and cell-related diseases.

  9. Biophysical characterization of the Lactobacillus delbrueckii subsp. bulgaricus membrane during cold and osmotic stress and its relevance for cryopreservation.

    Science.gov (United States)

    Meneghel, Julie; Passot, Stéphanie; Dupont, Sébastien; Fonseca, Fernanda

    2017-02-01

    Freezing lactic acid bacteria often leads to cell death and loss of technological properties. Our objective was to provide an in-depth characterization of the biophysical properties of the Lactobacillus delbrueckii subsp. bulgaricus membrane in relation to its freeze resistance. Freezing was represented as a combination of cold and osmotic stress. This work investigated the relative incidence of increasing sucrose concentrations coupled or not with subzero temperatures without ice nucleation on the biological and biophysical responses of two strains with different membrane fatty acid compositions and freeze resistances. Following exposure of bacterial cells to the highest sucrose concentration, the sensitive strain exhibited a survival rate of less than 10 % and 5 h of acidifying activity loss. Similar biological activity losses were observed upon freeze-thawing and after osmotic treatment for each strain thus highlighting osmotic stress as the main source of cryoinjury. The direct measurement of membrane fluidity by fluorescence anisotropy was linked to membrane lipid organization characterized by FTIR spectroscopy. Both approaches made it possible to investigate the specific contributions of the membrane core and the bilayer external surface to cell degradation caused by cold and osmotic stress. Cold-induced membrane rigidification had no significant implication on bacterial freeze-thaw resistance. Interactions between extracellular sucrose and membrane phospholipid headgroups under osmotic stress were also observed. Such interactions were more evident in the sensitive strain and when increasing sucrose concentration, thus suggesting membrane permeabilization. The relevance of biophysical properties for elucidating mechanisms of cryoinjury and cryoprotection is discussed.

  10. Biophysics An Introduction

    CERN Document Server

    Glaser, Roland

    2012-01-01

    Biophysics is the science of physical principles underlying all processes of life, including the dynamics and kinetics of biological systems. This fully revised 2nd English edition is an introductory text that spans all steps of biological organization, from the molecular, to the organism level, as well as influences of environmental factors. In response to the enormous progress recently made, especially in theoretical and molecular biophysics, the author has updated the text, integrating new results and developments concerning protein folding and dynamics, molecular aspects of membrane assembly and transport, noise-enhanced processes, and photo-biophysics. The advances made in theoretical biology in the last decade call for a fully new conception of the corresponding sections. Thus, the book provides the background needed for fundamental training in biophysics and, in addition, offers a great deal of advanced biophysical knowledge.

  11. Biophysics

    CERN Document Server

    Glaser, Roland

    1999-01-01

    The message of this book is that biophysics is the science of physical principles underlying the "phenomenon life" on all levels of organization. Rather than teaching "physics for biologists" or "physical methods applied to biology", it regards its subject as a defined discipline with its own network of ideas and approaches. The book starts by explaining molecular structures of biological systems, various kinds of atomic, molecular and ionic interactions, movements, energy transfer, self organization of supramolecular structures and dynamic properties of biological membranes. It then goes on to introduce the biological organism as a non-equilibrium system, before treating thermodynamic concepts of osmotic and electrolyte equilibria as well as currents and potential profiles. It continues with topics of environmental biophysics and such medical aspects as the influence of electromagnetic fields or radiation on living systems and the biophysics of hearing and noice protection. The book concludes with a discussi...

  12. Integrated Molecular and Cellular Biophysics

    CERN Document Server

    Raicu, Valerica

    2008-01-01

    This book integrates concepts and methods from physics, biology, biochemistry and physical chemistry into a standalone, unitary text of biophysics that aims to provide a quantitative description of structures and processes occurring in living matter. The book introduces graduate physics students and physicists interested in biophysics research to 'classical' as well as emerging areas of biophysics. The advanced undergraduate physics students and the life scientists are also invited to join in, by building on their knowledge of basic physics. Essential notions of biochemistry and biology are introduced, as necessary, throughout the book, while the reader's familiarity with basic knowledge of physics is assumed. Topics covered include interactions between biological molecules, physical chemistry of phospholipids association into bilayer membranes, DNA and protein structure and folding, passive and active electrical properties of the cell membrane, classical as well as fractal aspects of reaction kinetics and di...

  13. Encyclopedia of biophysics

    CERN Document Server

    2013-01-01

    The Encyclopedia of Biophysics is envisioned both as an easily accessible source of information and as an introductory guide to the scientific literature. It includes entries describing both Techniques and Systems.  In the Techniques entries, each of the wide range of methods which fall under the heading of Biophysics are explained in detail, together with the value and the limitations of the information each provides. Techniques covered range from diffraction (X-ray, electron and neutron) through a wide range of spectroscopic methods (X-ray, optical, EPR, NMR) to imaging (from electron microscopy to live cell imaging and MRI), as well as computational and simulation approaches. In the Systems entries, biophysical approaches to specific biological systems or problems – from protein and nucleic acid structure to membranes, ion channels and receptors – are described. These sections, which place emphasis on the integration of the different techniques, therefore provide an inroad into Biophysics from a biolo...

  14. Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies

    Science.gov (United States)

    2018-01-01

    Membrane proteins perform a host of vital cellular functions. Deciphering the molecular mechanisms whereby they fulfill these functions requires detailed biophysical and structural investigations. Detergents have proven pivotal to extract the protein from its native surroundings. Yet, they provide a milieu that departs significantly from that of the biological membrane, to the extent that the structure, the dynamics, and the interactions of membrane proteins in detergents may considerably vary, as compared to the native environment. Understanding the impact of detergents on membrane proteins is, therefore, crucial to assess the biological relevance of results obtained in detergents. Here, we review the strengths and weaknesses of alkyl phosphocholines (or foscholines), the most widely used detergent in solution-NMR studies of membrane proteins. While this class of detergents is often successful for membrane protein solubilization, a growing list of examples points to destabilizing and denaturing properties, in particular for α-helical membrane proteins. Our comprehensive analysis stresses the importance of stringent controls when working with this class of detergents and when analyzing the structure and dynamics of membrane proteins in alkyl phosphocholine detergents. PMID:29488756

  15. Biophysical shunt theory for neuropsychopathology: Part I.

    Science.gov (United States)

    Naisberg, Y; Avnon, M; Weizman, A

    1995-11-01

    We present a new model of the origin of schizophrenia based on biophysical ionic shunts in neuronal (electrical) pathways. Microstructural and molecular evidence is presented for the way in which changes in the neuronal membrane ionic channels may facilitate membrane property rearrangement, leading to a change in the density and composition of the ion channel charge which in turn causes a change in ionic flow orientation and distribution. We suggest that, under abnormal conditions, ionic flow shunts are created which redirect the biophysical collateral neuronal (electrical) pathways, resulting in psychiatric signs and symptoms. This model is complementary to the biological basis of schizophrenia.

  16. Mathematical biophysics

    CERN Document Server

    Rubin, Andrew

    2014-01-01

    This book presents concise descriptions and analysis of the classical and modern models used in mathematical biophysics. The authors ask the question "what new information can be provided by the models that cannot be obtained directly from experimental data?" Actively developing fields such as regulatory mechanisms in cells and subcellular systems and electron transport and energy transport in membranes are addressed together with more classical topics such as metabolic processes, nerve conduction and heart activity, chemical kinetics, population dynamics, and photosynthesis. The main approach is to describe biological processes using different mathematical approaches necessary to reveal characteristic features and properties of simulated systems. With the emergence of powerful mathematics software packages such as MAPLE, Mathematica, Mathcad, and MatLab, these methodologies are now accessible to a wide audience. Provides succinct but authoritative coverage of a broad array of biophysical topics and models Wr...

  17. Structure-function relationships in pulmonary surfactant membranes: from biophysics to therapy.

    Science.gov (United States)

    Lopez-Rodriguez, Elena; Pérez-Gil, Jesús

    2014-06-01

    Pulmonary surfactant is an essential lipid-protein complex to maintain an operative respiratory surface at the mammalian lungs. It reduces surface tension at the alveolar air-liquid interface to stabilise the lungs against physical forces operating along the compression-expansion breathing cycles. At the same time, surfactant integrates elements establishing a primary barrier against the entry of pathogens. Lack or deficiencies of the surfactant system are associated with respiratory pathologies, which treatment often includes supplementation with exogenous materials. The present review summarises current models on the molecular mechanisms of surfactant function, with particular emphasis in its biophysical properties to stabilise the lungs and the molecular alterations connecting impaired surfactant with diseased organs. It also provides a perspective on the current surfactant-based strategies to treat respiratory pathologies. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Biophysical characteristics reveal neural stem cell differentiation potential.

    Directory of Open Access Journals (Sweden)

    Fatima H Labeed

    Full Text Available Distinguishing human neural stem/progenitor cell (huNSPC populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers.We used dielectrophoresis (DEP to analyze the biophysical, specifically electrophysiological, properties of cortical human and mouse NSPCs that vary in differentiation potential. Our data demonstrate that the electrophysiological property membrane capacitance inversely correlates with the neurogenic potential of NSPCs. Furthermore, as huNSPCs are continually passaged they decrease neuron generation and increase membrane capacitance, confirming that this parameter dynamically predicts and negatively correlates with neurogenic potential. In contrast, differences in membrane conductance between NSPCs do not consistently correlate with the ability of the cells to generate neurons. DEP crossover frequency, which is a quantitative measure of cell behavior in DEP, directly correlates with neuron generation of NSPCs, indicating a potential mechanism to separate stem cells biased to particular differentiated cell fates.We show here that whole cell membrane capacitance, but not membrane conductance, reflects and predicts the neurogenic potential of human and mouse NSPCs. Stem cell biophysical characteristics therefore provide a completely novel and quantitative measure of stem cell fate potential and a label-free means to identify neuron- or glial-biased progenitors.

  19. Biophysical parameters of erythrocyte membranes and mechanisms of interaction with non-opioid analgesics under acute pain syndrome

    Directory of Open Access Journals (Sweden)

    Yu. I. Gubskyi

    2014-06-01

    Full Text Available Methods of fluorescent probing, spectrophotometry and microcalorimetry were applied to investigate the alterations in biophysical parameters of erythrocytes membranes, and specifically microviscosity, surface charge, molecular organization of lipid bilayer and lipid-protein interactions under conditions of acute pain syndrome produced by experimental chemical lesion. The distinctive features of non-opiod analgesics interactions and binding to the erythrocytes membranes of rats subjected to acute nociceptive pain accompanied with oxidative stress development were investigated. The abilities of analgesics under research, and namely paracetamol, aspirin, phenazone, ketorolac, pyrodazole, ketoprofenum, natrium mefenaminate, indometacin, nimesulide to make up physico-chemical complexes with lipoperoxidation modified erythrocytes surface and protein-lipid bilayer showed marked changes. The significance of oxidative damage of biophase under conditions of acute pain syndrome for analgesics effective pharmacodynamics and pharmacokinetics realization is under consideration.

  20. Online determination of biophysical parameters of mucous membranes of a human body

    Energy Technology Data Exchange (ETDEWEB)

    Lisenko, S A; Kugeiko, M M [Belarusian State University, Minsk (Belarus)

    2013-07-31

    We have developed a method for online determination of biophysical parameters of mucous membranes (MMs) of a human body (transport scattering coefficient, scattering anisotropy factor, haemoglobin concentration, degrees of blood oxygenation, average diameter of capillaries with blood) from measurements of spectral and spatial characteristics of diffuse reflection. The method is based on regression relationships between linearly independent components of the measured light signals and the unknown parameters of MMs, obtained by simulation of the radiation transfer in the MM under conditions of its general variability. We have proposed and justified the calibration-free fibre-optic method for determining the concentration of haemoglobin in MMs by measuring the light signals diffusely reflected by the tissue in four spectral regions at two different distances from the illumination spot. We have selected the optimal wavelengths of optical probing for the implementation of the method. (laser applications in biology and medicine)

  1. Biophysical Insights into How Spike Threshold Depends on the Rate of Membrane Potential Depolarization in Type I and Type II Neurons.

    Directory of Open Access Journals (Sweden)

    Guo-Sheng Yi

    Full Text Available Dynamic spike threshold plays a critical role in neuronal input-output relations. In many neurons, the threshold potential depends on the rate of membrane potential depolarization (dV/dt preceding a spike. There are two basic classes of neural excitability, i.e., Type I and Type II, according to input-output properties. Although the dynamical and biophysical basis of their spike initiation has been established, the spike threshold dynamic for each cell type has not been well described. Here, we use a biophysical model to investigate how spike threshold depends on dV/dt in two types of neuron. It is observed that Type II spike threshold is more depolarized and more sensitive to dV/dt than Type I. With phase plane analysis, we show that each threshold dynamic arises from the different separatrix and K+ current kinetics. By analyzing subthreshold properties of membrane currents, we find the activation of hyperpolarizing current prior to spike initiation is a major factor that regulates the threshold dynamics. The outward K+ current in Type I neuron does not activate at the perithresholds, which makes its spike threshold insensitive to dV/dt. The Type II K+ current activates prior to spike initiation and there is a large net hyperpolarizing current at the perithresholds, which results in a depolarized threshold as well as a pronounced threshold dynamic. These predictions are further attested in several other functionally equivalent cases of neural excitability. Our study provides a fundamental description about how intrinsic biophysical properties contribute to the threshold dynamics in Type I and Type II neurons, which could decipher their significant functions in neural coding.

  2. Novicidin interactions with phospholipid membranes

    DEFF Research Database (Denmark)

    Balakrishnan, Vijay Shankar

    Antimicrobial peptides target bacterial cell membranes and are considered as potential antibiotics. Their interactions with cell membranes are studied using different approaches. This thesis comprises of the biophysical investigations on the antimicrobial peptide Novicidin, interacting with lipos......Antimicrobial peptides target bacterial cell membranes and are considered as potential antibiotics. Their interactions with cell membranes are studied using different approaches. This thesis comprises of the biophysical investigations on the antimicrobial peptide Novicidin, interacting...... with liposomes. The lipid-induced changes in the peptide due to membrane binding, and the peptide-induced changes in the membrane properties were investigated using various spectroscopic and calorimetric methods, and the structural and thermodynamic aspects of peptide-lipid interactions are discussed. This helps...

  3. Radiation biophysics

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    Summaries of research projects conducted during 1978 and 1979 are presented. The overall thrust of the research is aimed at understanding the effects of radiation on organisms. Specific subject areas include: the effects of heavy-particle beam nuclear interactions in tissue on dosimetry; tracer studies with radioactive fragments of heavy-ion beams; the effects of heavy/ions on human kidney cells and Chinese hamster cells; the response of a rhabdomyosarcoma tumor system in rats to heavy-ion beams; the use of heavy charged particles in radiotherapy of human cancer; heavy-ion radiography; the biological effects of high magnetic fields; central nervous system neurotoxicity; and biophysical studies on cell membranes

  4. Model cell membranes

    DEFF Research Database (Denmark)

    Günther-Pomorski, Thomas; Nylander, Tommy; Cardenas Gomez, Marite

    2014-01-01

    The high complexity of biological membranes has motivated the development and application of a wide range of model membrane systems to study biochemical and biophysical aspects of membranes in situ under well defined conditions. The aim is to provide fundamental understanding of processes control...

  5. The physical basis of biochemistry the foundations of molecular biophysics

    CERN Document Server

    Bergethon, Peter R

    1998-01-01

    The objective of this book is to provide a unifying approach to the study of biophysical chemistry for the advanced undergraduate who has had a year of physics, organic chem­ istry, calculus, and biology. This book began as a revised edition of Biophysical Chemistry: Molecules to Membranes, which Elizabeth Simons and I coauthored. That short volume was written in an attempt to provide a concise text for a one-semester course in biophysical chemistry at the graduate level. The experience of teaching biophysical chemistry to bi­ ologically oriented students over the last decade has made it clear that the subject requires a more fundamental text that unifies the many threads of modem science: physics, chem­ istry, biology, mathematics, and statistics. This book represents that effort. This volume is not a treatment of modem biophysical chemistry with its rich history and many contro­ versies, although a book on that topic is also needed. The Physical Basis of Biochemistry is an introduction to the philosophy...

  6. Biophysical and lipofection studies of DOTAP analogs.

    Science.gov (United States)

    Regelin, A E; Fankhaenel, S; Gürtesch, L; Prinz, C; von Kiedrowski, G; Massing, U

    2000-03-15

    In order to investigate the relationship between lipid structure and liposome-mediated gene transfer, we have studied biophysical parameters and transfection properties of monocationic DOTAP analogs, systematically modified in their non-polar hydrocarbon chains. Stability, size and (by means of anisotropy profiles) membrane fluidity of liposomes and lipoplexes were determined, and lipofection efficiency was tested in a luciferase reporter gene assay. DOTAP analogs were used as single components or combined with a helper lipid, either DOPE or cholesterol. Stability of liposomes was a precondition for formation of temporarily stable lipoplexes. Addition of DOPE or cholesterol improved liposome and lipoplex stability. Transfection efficiencies of lipoplexes based on pure DOTAP analogs could be correlated with stability data and membrane fluidity at transfection temperature. Inclusion of DOPE led to rather uniform transfection and anisotropy profiles, corresponding to lipoplex stability. Cholesterol-containing lipoplexes were generally stable, showing high transfection efficiency at low relative fluidity. Our results demonstrate that the efficiency of gene transfer mediated by monocationic lipids is greatly influenced by lipoplex biophysics due to lipid composition. The measurement of fluorescence anisotropy is an appropriate method to characterize membrane fluidity within a defined system of liposomes or lipoplexes and may be helpful to elucidate structure-activity relationships.

  7. Biophysical characterization and membrane interaction of the two fusion loops of glycoprotein B from herpes simplex type I virus.

    Directory of Open Access Journals (Sweden)

    Annarita Falanga

    Full Text Available The molecular mechanism of entry of herpesviruses requires a multicomponent fusion system. Cell invasion by Herpes simplex virus (HSV requires four virally encoded glycoproteins: namely gD, gB and gH/gL. The role of gB has remained elusive until recently when the crystal structure of HSV-1 gB became available and the fusion potential of gB was clearly demonstrated. Although much information on gB structure/function relationship has been gathered in recent years, the elucidation of the nature of the fine interactions between gB fusion loops and the membrane bilayer may help to understand the precise molecular mechanism behind herpesvirus-host cell membrane fusion. Here, we report the first biophysical study on the two fusion peptides of gB, with a particular focus on the effects determined by both peptides on lipid bilayers of various compositions. The two fusion loops constitute a structural subdomain wherein key hydrophobic amino acids form a ridge that is supported on both sides by charged residues. When used together the two fusion loops have the ability to significantly destabilize the target membrane bilayer, notwithstanding their low bilayer penetration when used separately. These data support the model of gB fusion loops insertion into cholesterol enriched membranes.

  8. Engineered biomaterial and biophysical stimulation as combinatorial strategies to address prosthetic infection by pathogenic bacteria.

    Science.gov (United States)

    Boda, Sunil Kumar; Basu, Bikramjit

    2017-10-01

    A plethora of antimicrobial strategies are being developed to address prosthetic infection. The currently available methods for implant infection treatment include the use of antibiotics and revision surgery. Among the bacterial strains, Staphylococcus species pose significant challenges particularly, with regard to hospital acquired infections. In order to combat such life threatening infectious diseases, researchers have developed implantable biomaterials incorporating nanoparticles, antimicrobial reinforcements, surface coatings, slippery/non-adhesive and contact killing surfaces. This review discusses a few of the biomaterial and biophysical antimicrobial strategies, which are in the developmental stage and actively being pursued by several research groups. The clinical efficacy of biophysical stimulation methods such as ultrasound, electric and magnetic field treatments against prosthetic infection depends critically on the stimulation protocol and parameters of the treatment modality. A common thread among the three biophysical stimulation methods is the mechanism of bactericidal action, which is centered on biophysical rupture of bacterial membranes, the generation of reactive oxygen species (ROS) and bacterial membrane depolarization evoked by the interference of essential ion-transport. Although the extent of antimicrobial effect, normally achieved through biophysical stimulation protocol is insufficient to warrant therapeutic application, a combination of antibiotic/ROS inducing agents and biophysical stimulation methods can elicit a clinically relevant reduction in viable bacterial numbers. In this review, we present a detailed account of both the biomaterial and biophysical approaches for achieving maximum bacterial inactivation. Summarizing, the biophysical stimulation methods in a combinatorial manner with material based strategies can be a more potent solution to control bacterial infections. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B

  9. Melatonin reverses the enhanced oxidative damage to membrane lipids and improves skin biophysical characteristics in former-smokers - A study in postmenopausal women.

    Science.gov (United States)

    Sagan, Dorota; Stepniak, Jan; Gesing, Adam; Lewinski, Andrzej; Karbownik-Lewinska, Malgorzata

    2017-12-23

    Protective antioxidative effects of melatonin have been repeatedly documented in experimental and clinical studies. One of the most spectacular exogenous prooxidative agents is cigarette smoking. The aim of the study was to evaluate the level of oxidative damage to membrane lipids (lipid peroxidation; LPO) in blood serum, and in epidermis exfoliated during microdermabrasion collected from former-smokers who were treated with melatonin. The study was performed in postmenopausal women. Ninety (90) female volunteers, aged 46-67 years, were enrolled. Two major groups, i.e. never-smokers (n=44) and former-smokers (n=46), were divided into: Control, melatonin topical skin application, Restructurer (containing antioxidants) topical skin application, and melatonin oral treatment. Microdermabrasion was performed at point '0', after 2 weeks, and after 4 weeks of treatment. The following parameters were measured: LPO in blood serum, LPO in epidermis exfoliated during microdermabrasion, and skin biophysical characteristics, such as sebum, moisture, elasticity, and pigmentation. Malondialdehyde+4-hydroxyalkenals level (LPO index) was measured spectrophotometrically. Melatonin oral treatment significantly reversed the increased serum LPO level in former-smokers already after 2 weeks of treatment. In a univariate regression model, LPO blood level constituted the only independent factor negatively associated with melatonin oral treatment. After 4 weeks of treatment, melatonin given orally increased skin sebum, moisture and elasticity levels, and melatonin applied topically increased sebum level. Exogenous melatonin reverses the enhanced oxidative damage to membrane lipids and improves skin biophysical characteristics in former-smokers.

  10. Biophysics of protein evolution and evolutionary protein biophysics

    Science.gov (United States)

    Sikosek, Tobias; Chan, Hue Sun

    2014-01-01

    The study of molecular evolution at the level of protein-coding genes often entails comparing large datasets of sequences to infer their evolutionary relationships. Despite the importance of a protein's structure and conformational dynamics to its function and thus its fitness, common phylogenetic methods embody minimal biophysical knowledge of proteins. To underscore the biophysical constraints on natural selection, we survey effects of protein mutations, highlighting the physical basis for marginal stability of natural globular proteins and how requirement for kinetic stability and avoidance of misfolding and misinteractions might have affected protein evolution. The biophysical underpinnings of these effects have been addressed by models with an explicit coarse-grained spatial representation of the polypeptide chain. Sequence–structure mappings based on such models are powerful conceptual tools that rationalize mutational robustness, evolvability, epistasis, promiscuous function performed by ‘hidden’ conformational states, resolution of adaptive conflicts and conformational switches in the evolution from one protein fold to another. Recently, protein biophysics has been applied to derive more accurate evolutionary accounts of sequence data. Methods have also been developed to exploit sequence-based evolutionary information to predict biophysical behaviours of proteins. The success of these approaches demonstrates a deep synergy between the fields of protein biophysics and protein evolution. PMID:25165599

  11. Biophysical and biochemical strategies to understand membrane binding and pore formation by sticholysins, pore-forming proteins from a sea anemone.

    Science.gov (United States)

    Alvarez, Carlos; Ros, Uris; Valle, Aisel; Pedrera, Lohans; Soto, Carmen; Hervis, Yadira P; Cabezas, Sheila; Valiente, Pedro A; Pazos, Fabiola; Lanio, Maria E

    2017-10-01

    Actinoporins constitute a unique class of pore-forming toxins found in sea anemones that are able to bind and oligomerize in membranes, leading to cell swelling, impairment of ionic gradients and, eventually, to cell death. In this review we summarize the knowledge generated from the combination of biochemical and biophysical approaches to the study of sticholysins I and II (Sts, StI/II), two actinoporins largely characterized by the Center of Protein Studies at the University of Havana during the last 20 years. These approaches include strategies for understanding the toxin structure-function relationship, the protein-membrane association process leading to pore formation and the interaction of toxin with cells. The rational combination of experimental and theoretical tools have allowed unraveling, at least partially, of the complex mechanisms involved in toxin-membrane interaction and of the molecular pathways triggered upon this interaction. The study of actinoporins is important not only to gain an understanding of their biological roles in anemone venom but also to investigate basic molecular mechanisms of protein insertion into membranes, protein-lipid interactions and the modulation of protein conformation by lipid binding. A deeper knowledge of the basic molecular mechanisms involved in Sts-cell interaction, as described in this review, will support the current investigations conducted by our group which focus on the design of immunotoxins against tumor cells and antigen-releasing systems to cell cytosol as Sts-based vaccine platforms.

  12. Ninth International Workshop on Plant Membrane Biology

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-31

    This report is a compilation of abstracts from papers which were discussed at a workshop on plant membrane biology. Topics include: plasma membrane ATP-ases; plant-environment interactions, membrane receptors; signal transduction; ion channel physiology; biophysics and molecular biology; vaculor H+ pumps; sugar carriers; membrane transport; and cellular structure and function.

  13. Epigenetic modulation of the biophysical properties of drug-resistant cell lipids to restore drug transport and endocytic functions.

    Science.gov (United States)

    Vijayaraghavalu, Sivakumar; Peetla, Chiranjeevi; Lu, Shan; Labhasetwar, Vinod

    2012-09-04

    In our recent studies exploring the biophysical characteristics of resistant cell lipids, and the role they play in drug transport, we demonstrated the difference of drug-resistant breast cancer cells from drug-sensitive cells in lipid composition and biophysical properties, suggesting that cancer cells acquire a drug-resistant phenotype through the alteration of lipid synthesis to inhibit intracellular drug transport to protect from cytotoxic effect. In cancer cells, epigenetic changes (e.g., DNA hypermethylation) are essential to maintain this drug-resistant phenotype. Thus, altered lipid synthesis may be linked to epigenetic mechanisms of drug resistance. We hypothesize that reversing DNA hypermethylation in resistant cells with an epigenetic drug could alter lipid synthesis, changing the cell membrane's biophysical properties to facilitate drug delivery to overcome drug resistance. Herein we show that treating drug-resistant breast cancer cells (MCF-7/ADR) with the epigenetic drug 5-aza-2'-deoxycytidine (decitabine) significantly alters cell lipid composition and biophysical properties, causing the resistant cells to acquire biophysical characteristics similar to those of sensitive cell (MCF-7) lipids. Following decitabine treatment, resistant cells demonstrated increased sphingomyelinase activity, resulting in a decreased sphingomyelin level that influenced lipid domain structures, increased membrane fluidity, and reduced P-glycoprotein expression. Changes in the biophysical characteristics of resistant cell lipids facilitated doxorubicin transport and restored endocytic function for drug delivery with a lipid-encapsulated form of doxorubicin, enhancing the drug efficacy. In conclusion, we have established a new mechanism for efficacy of an epigenetic drug, mediated through changes in lipid composition and biophysical properties, in reversing cancer drug resistance.

  14. Reorganization of plasma membrane lipid domains during conidial germination.

    Science.gov (United States)

    Santos, Filipa C; Fernandes, Andreia S; Antunes, Catarina A C; Moreira, Filipe P; Videira, Arnaldo; Marinho, H Susana; de Almeida, Rodrigo F M

    2017-02-01

    Neurospora crassa, a filamentous fungus, in the unicellular conidial stage has ideal features to study sphingolipid (SL)-enriched domains, which are implicated in fundamental cellular processes ranging from antifungal resistance to apoptosis. Several changes in lipid metabolism and in the membrane composition of N. crassa occur during spore germination. However, the biophysical impact of those changes is unknown. Thus, a biophysical study of N. crassa plasma membrane, particularly SL-enriched domains, and their dynamics along conidial germination is prompted. Two N. crassa strains, wild-type (WT) and slime, which is devoid of cell wall, were studied. Conidial growth of N. crassa WT from a dormancy state to an exponential phase was accompanied by membrane reorganization, namely an increase of membrane fluidity, occurring faster in a supplemented medium than in Vogel's minimal medium. Gel-like domains, likely enriched in SLs, were found in both N. crassa strains, but were particularly compact, rigid and abundant in the case of slime cells, even more than in budding yeast Saccharomyces cerevisiae. In N. crassa, our results suggest that the melting of SL-enriched domains occurs near growth temperature (30°C) for WT, but at higher temperatures for slime. Regarding biophysical properties strongly affected by ergosterol, the plasma membrane of slime conidia lays in between those of N. crassa WT and S. cerevisiae cells. The differences in biophysical properties found in this work, and the relationships established between membrane lipid composition and dynamics, give new insights about the plasma membrane organization and structure of N. crassa strains during conidial growth. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Structural and biophysical characterization of an epitope-specific engineered Fab fragment and complexation with membrane proteins: implications for co-crystallization.

    Science.gov (United States)

    Johnson, Jennifer L; Entzminger, Kevin C; Hyun, Jeongmin; Kalyoncu, Sibel; Heaner, David P; Morales, Ivan A; Sheppard, Aly; Gumbart, James C; Maynard, Jennifer A; Lieberman, Raquel L

    2015-04-01

    Crystallization chaperones are attracting increasing interest as a route to crystal growth and structure elucidation of difficult targets such as membrane proteins. While strategies to date have typically employed protein-specific chaperones, a peptide-specific chaperone to crystallize multiple cognate peptide epitope-containing client proteins is envisioned. This would eliminate the target-specific chaperone-production step and streamline the co-crystallization process. Previously, protein engineering and directed evolution were used to generate a single-chain variable (scFv) antibody fragment with affinity for the peptide sequence EYMPME (scFv/EE). This report details the conversion of scFv/EE to an anti-EE Fab format (Fab/EE) followed by its biophysical characterization. The addition of constant chains increased the overall stability and had a negligible impact on the antigen affinity. The 2.0 Å resolution crystal structure of Fab/EE reveals contacts with larger surface areas than those of scFv/EE. Surface plasmon resonance, an enzyme-linked immunosorbent assay, and size-exclusion chromatography were used to assess Fab/EE binding to EE-tagged soluble and membrane test proteins: namely, the β-barrel outer membrane protein intimin and α-helical A2a G protein-coupled receptor (A2aR). Molecular-dynamics simulation of the intimin constructs with and without Fab/EE provides insight into the energetic complexities of the co-crystallization approach.

  16. Editorial: Molecular Organization of Membranes: Where Biology Meets Biophysics

    Czech Academy of Sciences Publication Activity Database

    Cebecauer, Marek; Holowka, D.

    2017-01-01

    Roč. 5, č. 113 (2017), s. 1-3 ISSN 2296-634X Institutional support: RVO:61388955 Keywords : nanodomains * membrane properties * cell membrane Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology

  17. Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a Molecular Adjuvant.

    Science.gov (United States)

    Ivey, Jill W; Latouche, Eduardo L; Richards, Megan L; Lesser, Glenn J; Debinski, Waldemar; Davalos, Rafael V; Verbridge, Scott S

    2017-07-25

    Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration. However, we have recently demonstrated that the nuclear/cytoplasm ratio (NCR), rather than cell size, is a key predictor of response for cells treated with high-frequency irreversible electroporation (IRE). In this study, we leverage a targeted molecular therapy, ephrinA1, known to markedly collapse the cytoplasm of cells expressing the EphA2 receptor, to investigate how biophysical cellular changes resulting from NCR manipulation affect the response to IRE at varying frequencies. We present evidence that the increase in the NCR mitigates the cell death response to conventional electroporation pulsed-electric fields (∼100 μs), consistent with the previously noted size dependence. However, this same molecular treatment enhanced the cell death response to high-frequency electric fields (∼1 μs). This finding demonstrates the importance of considering cellular biophysics and frequency-dependent effects in developing electroporation protocols, and our approach provides, to our knowledge, a novel and direct experimental methodology to quantify the relationship between cell morphology, pulse frequency, and electroporation response. Finally, this novel, to our knowledge, combinatorial approach may provide a paradigm to enhance in vivo tumor ablation through a molecular manipulation of cellular morphology before IRE application. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  18. Methods in Modern Biophysics

    CERN Document Server

    Nölting, Bengt

    2006-01-01

    Incorporating recent dramatic advances, this textbook presents a fresh and timely introduction to modern biophysical methods. An array of new, faster and higher-power biophysical methods now enables scientists to examine the mysteries of life at a molecular level. This innovative text surveys and explains the ten key biophysical methods, including those related to biophysical nanotechnology, scanning probe microscopy, X-ray crystallography, ion mobility spectrometry, mass spectrometry, proteomics, and protein folding and structure. Incorporating much information previously unavailable in tutorial form, Nölting employs worked examples and 267 illustrations to fully detail the techniques and their underlying mechanisms. Methods in Modern Biophysics is written for advanced undergraduate and graduate students, postdocs, researchers, lecturers and professors in biophysics, biochemistry and related fields. Special features in the 2nd edition: • Illustrates the high-resolution methods for ultrashort-living protei...

  19. Methods in Modern Biophysics

    CERN Document Server

    Nölting, Bengt

    2010-01-01

    Incorporating recent dramatic advances, this textbook presents a fresh and timely introduction to modern biophysical methods. An array of new, faster and higher-power biophysical methods now enables scientists to examine the mysteries of life at a molecular level. This innovative text surveys and explains the ten key biophysical methods, including those related to biophysical nanotechnology, scanning probe microscopy, X-ray crystallography, ion mobility spectrometry, mass spectrometry, proteomics, and protein folding and structure. Incorporating much information previously unavailable in tutorial form, Nölting employs worked examples and about 270 illustrations to fully detail the techniques and their underlying mechanisms. Methods in Modern Biophysics is written for advanced undergraduate and graduate students, postdocs, researchers, lecturers, and professors in biophysics, biochemistry and related fields. Special features in the 3rd edition: Introduces rapid partial protein ladder sequencing - an important...

  20. 19th International School of Biophysics "Ettore Majorana"

    CERN Document Server

    Blank, M; Bioelectrochemistry III : Charge Separation across Biomembranes

    1988-01-01

    This book contains aseries of review papers related to the lectures given at the Third Course on Bioelectrochemistry held at Erice in November 1988, in the framework of the International School of Biophysics. The topics covered by this course, "Charge Separation Across Biomembranes, " deal with the electrochemical aspects of some basic phenomena in biological systems, such as transport of ions, ATP synthesis, formation and maintenance of ionic and protonic gradients. In the first part of the course some preliminary lectures introduce the students to the most basic phenomena and technical aspects of membrane bioelectrochemistry. The remaining part of the course is devoted to the description of a selected group of membrane-enzyme systems, capable of promoting, or exploiting, the processes of separation of electrically charged entities (electrons or ions) across the membrane barrier. These systems are systematically discussed both from a structural and functional point of view. The effort of the many dis...

  1. Symposium on Biophysics and Physiology of Biological Transport

    CERN Document Server

    Capraro, V; Porter, K; Robertson, J

    1967-01-01

    The study of cell membranes began to attract increasing interest before the turn of the present century with the observations of 0 verton. Since that time many investigators have become interested in the broad problem of structure and function of the membrane and today we find ourselVes at a stage in which several branches of research, particularly physical chemistry, biochemistry, biophysics, physiology and pharmacology have come together, leading to the possibility of obtaining a better perspective of the overall problems. The purpose of this Symposium was to assemble in an orderly sequence representations of the knowledge of membranes achieved to date in the areas of the various disciplines. It was thought that to bring together many points of view on a problem should allow the conferees to see better what had been accomplished, what has been overlooked and what needs further development. It is to be hoped that efforts of this type have and will fulfill the desired purpose. This volume contains the majorit...

  2. Theoretical molecular biophysics

    CERN Document Server

    Scherer, Philipp O J

    2017-01-01

    This book gives an introduction to molecular biophysics. It starts from material properties at equilibrium related to polymers, dielectrics and membranes. Electronic spectra are developed for the understanding of elementary dynamic processes in photosynthesis including proton transfer and dynamics of molecular motors. Since the molecular structures of functional groups of bio-systems were resolved, it has become feasible to develop a theory based on the quantum theory and statistical physics with emphasis on the specifics of the high complexity of bio-systems. This introduction to molecular aspects of the field focuses on solvable models. Elementary biological processes provide as special challenge the presence of partial disorder in the structure which does not destroy the basic reproducibility of the processes. Apparently the elementary molecular processes are organized in a way to optimize the efficiency. Learning from nature by means exploring the relation between structure and function may even help to b...

  3. Cellular biophysics during freezing of rat and mouse sperm predicts post-thaw motility.

    Science.gov (United States)

    Hagiwara, Mie; Choi, Jeung Hwan; Devireddy, Ramachandra V; Roberts, Kenneth P; Wolkers, Willem F; Makhlouf, Antoine; Bischof, John C

    2009-10-01

    Though cryopreservation of mouse sperm yields good survival and motility after thawing, cryopreservation of rat sperm remains a challenge. This study was designed to evaluate the biophysics (membrane permeability) of rat in comparison to mouse to better understand the cooling rate response that contributes to cryopreservation success or failure in these two sperm types. In order to extract subzero membrane hydraulic permeability in the presence of ice, a differential scanning calorimeter (DSC) method was used. By analyzing rat and mouse sperm frozen at 5 degrees C/min and 20 degrees C/min, heat release signatures characteristic of each sperm type were obtained and correlated to cellular dehydration. The dehydration response was then fit to a model of cellular water transport (dehydration) by adjusting cell-specific biophysical (membrane hydraulic permeability) parameters L(pg) and E(Lp). A "combined fit" (to 5 degrees C/min and 20 degrees C/min data) for rat sperm in Biggers-Whitten-Whittingham media yielded L(pg) = 0.007 microm min(-1) atm(-1) and E(Lp) = 17.8 kcal/mol, and in egg yolk cryopreservation media yielded L(pg) = 0.005 microm min(-1) atm(-1) and E(Lp) = 14.3 kcal/mol. These parameters, especially the activation energy, were found to be lower than previously published parameters for mouse sperm. In addition, the biophysical responses in mouse and rat sperm were shown to depend on the constituents of the cryopreservation media, in particular egg yolk and glycerol. Using these parameters, optimal cooling rates for cryopreservation were predicted for each sperm based on a criteria of 5%-15% normalized cell water at -30 degrees C during freezing in cryopreservation media. These predicted rates range from 53 degrees C/min to 70 degrees C/min and from 28 degrees C/min to 36 degrees C/min in rat and mouse, respectively. These predictions were validated by comparison to experimentally determined cryopreservation outcomes, in this case based on motility. Maximum

  4. Membrane order in the plasma membrane and endocytic recycling compartment.

    Science.gov (United States)

    Iaea, David B; Maxfield, Frederick R

    2017-01-01

    The cholesterol content of membranes plays an important role in organizing membranes for signal transduction and protein trafficking as well as in modulating the biophysical properties of membranes. While the properties of model or isolated membranes have been extensively studied, there has been little evaluation of internal membranes in living cells. Here, we use a Nile Red based probe, NR12S, and ratiometric live cell imaging, to analyze the membrane order of the plasma membrane and endocytic recycling compartment. We find that after a brief incubation to allow endocytosis, NR12S is distributed between the plasma membrane and the endocytic recycling compartment. The NR12S reports that the endocytic recycling compartment is more highly ordered than the plasma membrane. We also find that the plasma membrane and the endocytic recycling compartment are differentially affected by altering cellular cholesterol levels. The membrane order of the plasma membrane, but not the endocytic recycling compartment, is altered significantly when cellular cholesterol content is increased or decreased by 20%. These results demonstrate that changes in cellular cholesterol differentially alter membrane order within different organelles.

  5. A quantitative overview of biophysical forces impinging on neural function

    International Nuclear Information System (INIS)

    Mueller, Jerel K; Tyler, William J

    2014-01-01

    The fundamentals of neuronal membrane excitability are globally described using the Hodgkin-Huxley (HH) model. The HH model, however, does not account for a number of biophysical phenomena associated with action potentials or propagating nerve impulses. Physical mechanisms underlying these processes, such as reversible heat transfer and axonal swelling, have been compartmentalized and separately investigated to reveal neuronal activity is not solely influenced by electrical or biochemical factors. Instead, mechanical forces and thermodynamics also govern neuronal excitability and signaling. To advance our understanding of neuronal function and dysfunction, compartmentalized analyses of electrical, chemical, and mechanical processes need to be revaluated and integrated into more comprehensive theories. The present perspective is intended to provide a broad overview of biophysical forces that can influence neural function, but which have been traditionally underappreciated in neuroscience. Further, several examples where mechanical forces have been shown to exert their actions on nervous system development, signaling, and plasticity are highlighted to underscore their importance in sculpting neural function. By considering the collective actions of biophysical forces influencing neuronal activity, our working models can be expanded and new paradigms can be applied to the investigation and characterization of brain function and dysfunction. (topical review)

  6. Importance of the hexagonal lipid phase in biological membrane organisation

    Directory of Open Access Journals (Sweden)

    Juliette eJouhet

    2013-12-01

    Full Text Available Abstract:Domains are present in every natural membrane. They are characterised by a distinctive protein and/or lipid composition. Their size is highly variable from the nano- to the micrometer scale. The domains confer specific properties to the membrane leading to original structure and function. The determinants leading to domain organisation are therefore important but remain obscure. This review presents how the ability of lipids to organize into hexagonal II or lamellar phases can promote particular local structures within membranes. Since biological membranes are composed of a mixture of lipids, each with distinctive biophysical properties, lateral and transversal sorting of lipids can promote creation of domains inside the membrane through local modulation of the lipid phase. Lipid biophysical properties have been characterized for long based on in vitro analyses using non-natural lipid molecules; their re-examinations using natural lipids might open interesting perspectives on membrane architecture occurring in vivo in various cellular and physiological contexts.

  7. Importance of the hexagonal lipid phase in biological membrane organization.

    Science.gov (United States)

    Jouhet, Juliette

    2013-01-01

    Domains are present in every natural membrane. They are characterized by a distinctive protein and/or lipid composition. Their size is highly variable from the nano- to the micrometer scale. The domains confer specific properties to the membrane leading to original structure and function. The determinants leading to domain organization are therefore important but remain obscure. This review presents how the ability of lipids to organize into hexagonal II or lamellar phases can promote particular local structures within membranes. Since biological membranes are composed of a mixture of lipids, each with distinctive biophysical properties, lateral and transversal sorting of lipids can promote creation of domains inside the membrane through local modulation of the lipid phase. Lipid biophysical properties have been characterized for long based on in vitro analyses using non-natural lipid molecules; their re-examinations using natural lipids might open interesting perspectives on membrane architecture occurring in vivo in various cellular and physiological contexts.

  8. 2. biophysical work meeting

    International Nuclear Information System (INIS)

    1992-11-01

    The report comprises 18 papers held at the 2nd Biophysical Work Meeting, 11 - 13 September 1991 in Schlema, Germany. The history of biophysics in Germany particularly of radiation biophysics and radon research, measurements of the radiation effects of radon and the derivation of limits, radon balneotherapy and consequences of uranium ore mining are dealt with. (orig.) [de

  9. Cellular Biophysics During Freezing of Rat and Mouse Sperm Predicts Post-thaw Motility1

    Science.gov (United States)

    Hagiwara, Mie; Choi, Jeung Hwan; Devireddy, Ramachandra V.; Roberts, Kenneth P.; Wolkers, Willem F.; Makhlouf, Antoine; Bischof, John C.

    2009-01-01

    Though cryopreservation of mouse sperm yields good survival and motility after thawing, cryopreservation of rat sperm remains a challenge. This study was designed to evaluate the biophysics (membrane permeability) of rat in comparison to mouse to better understand the cooling rate response that contributes to cryopreservation success or failure in these two sperm types. In order to extract subzero membrane hydraulic permeability in the presence of ice, a differential scanning calorimeter (DSC) method was used. By analyzing rat and mouse sperm frozen at 5°C/min and 20°C/min, heat release signatures characteristic of each sperm type were obtained and correlated to cellular dehydration. The dehydration response was then fit to a model of cellular water transport (dehydration) by adjusting cell-specific biophysical (membrane hydraulic permeability) parameters Lpg and ELp. A “combined fit” (to 5°C/min and 20°C/min data) for rat sperm in Biggers-Whitten-Whittingham media yielded Lpg = 0.007 μm min−1 atm−1 and ELp = 17.8 kcal/mol, and in egg yolk cryopreservation media yielded Lpg = 0.005 μm min−1 atm−1 and ELp = 14.3 kcal/mol. These parameters, especially the activation energy, were found to be lower than previously published parameters for mouse sperm. In addition, the biophysical responses in mouse and rat sperm were shown to depend on the constituents of the cryopreservation media, in particular egg yolk and glycerol. Using these parameters, optimal cooling rates for cryopreservation were predicted for each sperm based on a criteria of 5%–15% normalized cell water at −30°C during freezing in cryopreservation media. These predicted rates range from 53°C/min to 70°C/min and from 28°C/min to 36°C/min in rat and mouse, respectively. These predictions were validated by comparison to experimentally determined cryopreservation outcomes, in this case based on motility. Maximum motility was obtained with freezing rates between 50°C/min and 80

  10. Biophysical studies of cholesterol in unsaturated phospholipid model membranes

    Science.gov (United States)

    Williams, Justin Adam

    Cellular membranes contain a staggering diversity of lipids. The lipids are heterogeneously distributed to create regions, or domains, whose physical properties differ from the bulk membrane and play an essential role in modulating the function of resident proteins. Many basic questions pertaining to the formation of these lateral assemblies remain. This research employs model membranes of well-defined composition to focus on the potential role of polyunsaturated fatty acids (PUFAs) and their interaction with cholesterol (chol) in restructuring the membrane environment. Omega-3 (n-3) PUFAs are the main bioactive components of fish oil, whose consumption alleviates a variety of health problems by a molecular mechanism that is unclear. We hypothesize that the incorporation of PUFAs into membrane lipids and the effect they have on molecular organization may be, in part, responsible. Chol is a major constituent in the plasma membrane of mammals. It determines the arrangement and collective properties of neighboring lipids, driving the formation of domains via differential affinity for different lipids. The molecular organization of 1-[2H31]palmitoyl-2-eicosapentaenoylphosphatidylcholine (PEPC-d31) and 1-[2H31]palmitoyl-2-docosahexaenoylphosphatidylcholine (PDPC-d31) in membranes with sphingomyelin (SM) and chol (1:1:1 mol) was compared by solid-state 2H NMR spectroscopy. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are the two major n-3 PUFAs found in fish oil, while PEPC-d31 and PDPC-d31 are phospholipids containing the respective PUFAs at the sn-2 position and a perdeuterated palmitic acid at the sn-1 position. Analysis of spectra recorded as a function of temperature indicates that in both cases, formation of PUFA-rich (less ordered) and SM-rich (more ordered) domains occurred. A surprisingly substantial proportion of PUFA was found to infiltrate the more ordered domain. There was almost twice as much DHA (65%) as EPA (30%). The implication is that n-3

  11. Resolving the biophysics of axon transmembrane polarization in a single closed-form description

    Energy Technology Data Exchange (ETDEWEB)

    Melendy, Robert F., E-mail: rfmelendy@liberty.edu [School of Engineering and Computational Sciences, Liberty University, Lynchburg, Virginia 24515 (United States)

    2015-12-28

    When a depolarizing event occurs across a cell membrane there is a remarkable change in its electrical properties. A complete depolarization event produces a considerably rapid increase in voltage that propagates longitudinally along the axon and is accompanied by changes in axial conductance. A dynamically changing magnetic field is associated with the passage of the action potential down the axon. Over 75 years of research has gone into the quantification of this phenomenon. To date, no unified model exist that resolves transmembrane polarization in a closed-form description. Here, a simple but formative description of propagated signaling phenomena in the membrane of an axon is presented in closed-form. The focus is on using both biophysics and mathematical methods for elucidating the fundamental mechanisms governing transmembrane polarization. The results presented demonstrate how to resolve electromagnetic and thermodynamic factors that govern transmembrane potential. Computational results are supported by well-established quantitative descriptions of propagated signaling phenomena in the membrane of an axon. The findings demonstrate how intracellular conductance, the thermodynamics of magnetization, and current modulation function together in generating an action potential in a unified closed-form description. The work presented in this paper provides compelling evidence that three basic factors contribute to the propagated signaling in the membrane of an axon. It is anticipated this work will compel those in biophysics, physical biology, and in the computational neurosciences to probe deeper into the classical and quantum features of membrane magnetization and signaling. It is hoped that subsequent investigations of this sort will be advanced by the computational features of this model without having to resort to numerical methods of analysis.

  12. Biophysical aspects of using liposomes as delivery vehicles.

    Science.gov (United States)

    Ulrich, Anne S

    2002-04-01

    Liposomes are used as biocompatible carriers of drugs, peptides, proteins, plasmic DNA, antisense oligonucleotides or ribozymes, for pharmaceutical, cosmetic, and biochemical purposes. The enormous versatility in particle size and in the physical parameters of the lipids affords an attractive potential for constructing tailor-made vehicles for a wide range of applications. Some of the recent literature will be reviewed here and presented from a biophysical point of view, thus providing a background for the more specialized articles in this special issue on liposome technology. Different properties (size, colloidal behavior, phase transitions, and polymorphism) of diverse lipid formulations (liposomes, lipoplexes, cubic phases, emulsions, and solid lipid nanoparticles) for distinct applications (parenteral, transdermal, pulmonary, and oral administration) will be rationalized in terms of common structural, thermodynamic and kinetic parameters of the lipids. This general biophysical basis helps to understand pharmaceutically relevant aspects such as liposome stability during storage and towards serum, the biodistribution and specific targeting of cargo, and how to trigger drug release and membrane fusion. Methods for the preparation and characterization of liposomal formulations in vitro will be outlined, too.

  13. New horizons in Biophysics

    Science.gov (United States)

    2011-01-01

    This editorial celebrates the re-launch of PMC Biophysics previously published by PhysMath Central, in its new format as BMC Biophysics published by BioMed Central with an expanded scope and Editorial Board. BMC Biophysics will fill its own niche in the BMC series alongside complementary companion journals including BMC Bioinformatics, BMC Medical Physics, BMC Structural Biology and BMC Systems Biology. PMID:21595996

  14. Fundamental Concepts in Biophysics Volume 1

    CERN Document Server

    Jue, Thomas

    2009-01-01

    HANDBOOK OF MODERN BIOPHYSICS Series Editor Thomas Jue, PhD Handbook of Modern Biophysics brings current biophysics topics into focus, so that biology, medical, engineering, mathematics, and physical-science students or researchers can learn fundamental concepts and the application of new techniques in addressing biomedical challenges. Chapters explicate the conceptual framework of the physics formalism and illustrate the biomedical applications. With the addition of problem sets, guides to further study, and references, the interested reader can continue to explore independently the ideas presented. Volume I: Fundamental Concepts in Biophysics Editor Thomas Jue, PhD In Fundamental Concepts in Biophysics, prominent professors have established a foundation for the study of biophysics related to the following topics: Mathematical Methods in Biophysics Quantum Mechanics Basic to Biophysical Methods Computational Modeling of Receptor–Ligand Binding and Cellular Signaling Processes Fluorescence Spectroscopy Elec...

  15. A biophysical approach to the optimisation of dendritic-tumour cell electrofusion

    International Nuclear Information System (INIS)

    Sukhorukov, Vladimir L.; Reuss, Randolph; Endter, Joerg M.; Fehrmann, Steffen; Katsen-Globa, Alisa; Gessner, Petra; Steinbach, Andrea; Mueller, Kilian J.; Karpas, Abraham; Zimmermann, Ulrich; Zimmermann, Heiko

    2006-01-01

    Electrofusion of tumour and dendritic cells (DCs) is a promising approach for production of DC-based anti-tumour vaccines. Although human DCs are well characterised immunologically, little is known about their biophysical properties, including dielectric and osmotic parameters, both of which are essential for the development of efficient electrofusion protocols. In the present study, human DCs from the peripheral blood along with a tumour cell line used as a model fusion partner were examined by means of time-resolved cell volumetry and electrorotation. Based on the biophysical cell data, the electrofusion protocol could be rapidly optimised with respect to the sugar composition of the fusion medium, duration of hypotonic treatment, frequency range for stable cell alignment, and field strengths of breakdown pulses triggering membrane fusion. The hypotonic electrofusion consistently gave a tumour-DC hybrid rate of up to 19%, as determined by counting dually labelled fluorescent hybrids in a microscope. This fusion rate is nearly twice as high as that usually reported in the literature for isotonic media. The experimental findings and biophysical approach presented here are generally useful for the development of efficient electrofusion protocols, especially for rare and valuable human cells

  16. Biophysical characterization of membrane protein-small molecule interactions

    NARCIS (Netherlands)

    Chen, Dan

    2015-01-01

    Membrane proteins are account for up to two thirds of known druggable targets. Traditionally, new drugs against this class of proteins have been discovered through HTS. However, not all GPCRs are amenable to traditional screening methods. Recently, fragment-based drug discovery (FBDD) has emerged as

  17. Molecular Interactions at Membranes

    DEFF Research Database (Denmark)

    Jagalski, Vivien

    . Today, we know more than ever before about the properties of biological membranes. Advanced biophysical techniques and sophisticated membrane models allow us to answer specific questions about the structure of the components within membranes and their interactions. However, many detailed structural...... the surface-immobilization of LeuT by exchanging the detergent with natural phosphatidylcholine (PC) lipids. Various surface sensitive techniques, including neutron reflectometry (NR), are employed and finally enabled us to confirm the gross structure of LeuT in a lipid environment as predicted by molecular...... dynamic simulations. In a second study, the co-localization of three toxic plant-derived diterpene resin acids (RAs) within DPPC membranes was investigated. These compounds are reported to disrupt the membrane and increase its fluidity. The RAs used in this study vary in their toxicity while...

  18. Membrane properties involved in calcium-stimulated microparticle release from the plasma membranes of S49 lymphoma cells.

    Science.gov (United States)

    Campbell, Lauryl E; Nelson, Jennifer; Gibbons, Elizabeth; Judd, Allan M; Bell, John D

    2014-01-01

    This study answered the question of whether biophysical mechanisms for microparticle shedding discovered in platelets and erythrocytes also apply to nucleated cells: cytoskeletal disruption, potassium efflux, transbilayer phospholipid migration, and membrane disordering. The calcium ionophore, ionomycin, disrupted the actin cytoskeleton of S49 lymphoma cells and produced rapid release of microparticles. This release was significantly inhibited by interventions that impaired calcium-activated potassium current. Microparticle release was also greatly reduced in a lymphocyte cell line deficient in the expression of scramblase, the enzyme responsible for calcium-stimulated dismantling of the normal phospholipid transbilayer asymmetry. Rescue of the scrambling function at high ionophore concentration also resulted in enhanced particle shedding. The effect of membrane physical properties was addressed by varying the experimental temperature (32-42°C). A significant positive trend in the rate of microparticle release as a function of temperature was observed. Fluorescence experiments with trimethylammonium diphenylhexatriene and Patman revealed significant decrease in the level of apparent membrane order along that temperature range. These results demonstrated that biophysical mechanisms involved in microparticle release from platelets and erythrocytes apply also to lymphocytes.

  19. Metamaterial membranes

    International Nuclear Information System (INIS)

    Restrepo-Flórez, Juan Manuel; Maldovan, Martin

    2017-01-01

    We introduce a new class of metamaterial device to achieve separation of compounds by using coordinate transformations and metamaterial theory. By rationally designing the spatial anisotropy for mass diffusion, we simultaneously concentrate different compounds in different spatial locations, leading to separation of mixtures across a metamaterial membrane. The separation of mixtures into their constituent compounds is critically important in biophysics, biomedical, and chemical applications. We present a practical case where a mixture of oxygen and nitrogen diffusing through a polymeric planar matrix is separated. This work opens doors to new paradigms in membrane separations via coordinate transformations and metamaterials by introducing novel properties and unconventional mass diffusion phenomena. (paper)

  20. Quantum Nanobiology and Biophysical Chemistry

    DEFF Research Database (Denmark)

    2013-01-01

    An introduction was provided in the first issue by way of an Editorial to this special two issue volume of Current Physical Chemistry – “Quantum Nanobiology and Biophysical Chemistry” [1]. The Guest Editors would like to thank all the authors and referees who have contributed to this second issue....... Wu et al. use density functional theory to explore the use of Ni/Fe bimetallic nanotechnology in the bioremediation of decabromo-diphenyl esters. Araújo-Chaves et al. explore the binding and reactivity of Mn(III) porphyrins in the membrane mimetic setting of model liposomal systems. Claussen et al....... demonstrate extremely low detection performance of acyl-homoserine lactone in a biologically relevant system using surface enhanced Raman spectroscopy. Sugihara and Bondar evaluate the influence of methyl-groups and the protein environment on retinal geometries in rhodopsin and bacteriorhodopsin, two...

  1. Progress in surface and membrane science

    CERN Document Server

    Danielli, J F; Cadenhead, D A

    1973-01-01

    Progress in Surface and Membrane Science, Volume 6 covers the developments in the study of surface and membrane science. The book discusses the progress in surface and membrane science; the solid state chemistry of the silver halide surface; and the experimental and theoretical aspects of the double layer at the mercury-solution interface. The text also describes contact-angle hysteresis; ion binding and ion transport produced by neutral lipid-soluble molecules; and the biophysical interactions of blood proteins with polymeric and artificial surfaces. Physical chemists, biophysicists, and phys

  2. Biophysical mechanisms of endotoxin neutralization by cationic amphiphilic peptides.

    Science.gov (United States)

    Kaconis, Yani; Kowalski, Ina; Howe, Jörg; Brauser, Annemarie; Richter, Walter; Razquin-Olazarán, Iosu; Iñigo-Pestaña, Melania; Garidel, Patrick; Rössle, Manfred; Martinez de Tejada, Guillermo; Gutsmann, Thomas; Brandenburg, Klaus

    2011-06-08

    Bacterial endotoxins (lipopolysaccharides (LPS)) are strong elicitors of the human immune system by interacting with serum and membrane proteins such as lipopolysaccharide-binding protein (LBP) and CD14 with high specificity. At LPS concentrations as low as 0.3 ng/ml, such interactions may lead to severe pathophysiological effects, including sepsis and septic shock. One approach to inhibit an uncontrolled inflammatory reaction is the use of appropriate polycationic and amphiphilic antimicrobial peptides, here called synthetic anti-LPS peptides (SALPs). We designed various SALP structures and investigated their ability to inhibit LPS-induced cytokine secretion in vitro, their protective effect in a mouse model of sepsis, and their cytotoxicity in physiological human cells. Using a variety of biophysical techniques, we investigated selected SALPs with considerable differences in their biological responses to characterize and understand the mechanism of LPS inactivation by SALPs. Our investigations show that neutralization of LPS by peptides is associated with a fluidization of the LPS acyl chains, a strong exothermic Coulomb interaction between the two compounds, and a drastic change of the LPS aggregate type from cubic into multilamellar, with an increase in the aggregate sizes, inhibiting the binding of LBP and other mammalian proteins to the endotoxin. At the same time, peptide binding to phospholipids of human origin (e.g., phosphatidylcholine) does not cause essential structural changes, such as changes in membrane fluidity and bilayer structure. The absence of cytotoxicity is explained by the high specificity of the interaction of the peptides with LPS. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. Characterizing the structure of lipodisq nanoparticles for membrane protein spectroscopic studies.

    Science.gov (United States)

    Zhang, Rongfu; Sahu, Indra D; Liu, Lishan; Osatuke, Anna; Comer, Raven G; Dabney-Smith, Carole; Lorigan, Gary A

    2015-01-01

    Membrane protein spectroscopic studies are challenging due to the difficulty introduced in preparing homogenous and functional hydrophobic proteins incorporated into a lipid bilayer system. Traditional membrane mimics such as micelles or liposomes have proved to be powerful in solubilizing membrane proteins for biophysical studies, however, several drawbacks have limited their applications. Recently, a nanosized complex termed lipodisq nanoparticles was utilized as an alternative membrane mimic to overcome these caveats by providing a homogeneous lipid bilayer environment. Despite all the benefits that lipodisq nanoparticles could provide to enhance the biophysical studies of membrane proteins, structural characterization in different lipid compositions that closely mimic the native membrane environment is still lacking. In this study, the formation of lipodisq nanoparticles using different weight ratios of POPC/POPG lipids to SMA polymers was characterized via solid-state nuclear magnetic resonance (SSNMR) spectroscopy and dynamic light scattering (DLS). A critical weight ratio of (1/1.25) for the complete solubilization of POPC/POPG vesicles has been observed and POPC/POPG vesicles turned clear instantaneously upon the addition of the SMA polymer. The size of lipodisq nanoparticles formed from POPC/POPG lipids at this weight ratio of (1/1.25) was found to be about 30 nm in radius. We also showed that upon the complete solubilization of POPC/POPG vesicles by SMA polymers, the average size of the lipodisq nanoparticles is weight ratio dependent, when more SMA polymers were introduced, smaller lipodisq nanoparticles were obtained. The results of this study will be helpful for a variety of biophysical experiments when specific size of lipid disc is required. Further, this study will provide a proper path for researchers working on membrane proteins to obtain pertinent structure and dynamic information in a physiologically relevant membrane mimetic environment

  4. Advanced Techniques in Biophysics

    CERN Document Server

    Arrondo, José Luis R

    2006-01-01

    Technical advancements are basic elements in our life. In biophysical studies, new applications and improvements in well-established techniques are being implemented every day. This book deals with advancements produced not only from a technical point of view, but also from new approaches that are being taken in the study of biophysical samples, such as nanotechniques or single-cell measurements. This book constitutes a privileged observatory for reviewing novel applications of biophysical techniques that can help the reader enter an area where the technology is progressing quickly and where a comprehensive explanation is not always to be found.

  5. Plant membranes a biophysical approach to structure, development and senescence

    CERN Document Server

    Leshem, Ya’Acov Y

    1992-01-01

    The plasma membrane is at once the window through which the cell senses the environment and the portal through which the environment influences the structure and activities of the cell. Its importance in cellular physiology can thus hardly be overestimated, since constant flow of materials between cell and environment is essential to the well-being of any biological system. The nature of the materials mov­ ing into the cell is also critical, since some substances are required for maintenance and growth, while others, because of their toxicity, must either be rigorously excluded or permitted to enter only after chemical alteration. Such alteration frequently permits the compounds to be sequestered in special cellular compartments having different types of membranes. This type of homogeneity, plus the fact that the wear and tear of transmembrane molecular traffic compels the system to be constantly monitored and repaired, means that the membrane system of any organism must be both structurally complex and dy­...

  6. Proof of pore formation and biophysical perturbations through a 2D amoxicillin-lipid membrane interaction approach.

    Science.gov (United States)

    Lopes, Daniela; Nunes, Cláudia; Fontaine, Philippe; Sarmento, Bruno; Reis, Salette

    2017-05-01

    Amoxicillin is a worldwide used antibiotic, and it is classified as a first-line drug against Helicobacter pylori gastric infections. However, the current treatment of these infections has several limitations, such as the side effects and the low therapeutic compliance. Amoxicillin has been associated with gastrointestinal and renal side effects, with higher toxicity when the pH is lower. By considering this association and the well-known pH gradient of the gastric mucosa, this work aims to evaluate the influence of pH on the toxicity of amoxicillin. For that purpose, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayers were used since phosphatidylcholines are the most common phospholipid headgroup of biological membranes. To have insight of the effects of amoxicillin, different techniques were employed, namely, isotherm measurements, infrared reflection-absorption spectroscopy, grazing incident X-ray diffraction and Brewster angle microscopy. The monolayers of DPPC spread onto different buffer solutions (pH1.2, pH5 and pH7.4) showed different structural and packing properties. The interaction with amoxicillin also depended on the pH. At pH7.4, the highest effect was visualized at lower pressures, with partial restoration of the biophysical properties of the monolayer at 30 mN.m -1 . A higher perturbation is shown at acidic pH, in which pores were visualized by Brewster angle microscopy. These perturbations may ultimately be related with amoxicillin toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Translocation of cell penetrating peptides and calcium-induced membrane fusion share same mechanism

    Czech Academy of Sciences Publication Activity Database

    Magarkar, Aniket; Allolio, Christoph; Jurkiewicz, Piotr; Baxová, Katarína; Šachl, Radek; Horinek, D.; Heinz, V.; Rachel, R.; Ziegler, C.; Jungwirth, Pavel

    2017-01-01

    Roč. 46, Suppl 1 (2017), S386 ISSN 0175-7571. [IUPAB congress /19./ and EBSA congress /11./. 16.07.2017-20.07.2017, Edinburgh] Institutional support: RVO:61388963 ; RVO:61388955 Keywords : membrane interactions * membrane fusion * cell penetration Subject RIV: BO - Biophysics

  8. Life as a matter of fat : lipids in a membrane biophysics perspective

    CERN Document Server

    Mouritsen, Ole G

    2016-01-01

    The present book gives a multi-disciplinary perspective on the physics of life and the particular role played by lipids (fats) and the lipid-bilayer component of cell membranes. The emphasis is on the physical properties of lipid membranes seen as soft and molecularly structured interfaces. By combining and synthesizing insights obtained from a variety of recent studies, an attempt is made to clarify what membrane structure is and how it can be quantitatively described. Furthermore, it is shown how biological function mediated by membranes is controlled by lipid membrane structure and organization on length scales ranging from the size of the individual molecule, across molecular assemblies of proteins and lipid domains in the range of nanometers, to the size of whole cells. Applications of lipids in nanotechnology and biomedicine are also described.   The first edition of the present book was published in 2005 when lipidomics was still very much an emerging science and lipids about to be recognized as being...

  9. Biophysics of malarial parasite exit from infected erythrocytes.

    Science.gov (United States)

    Chandramohanadas, Rajesh; Park, YongKeun; Lui, Lena; Li, Ang; Quinn, David; Liew, Kingsley; Diez-Silva, Monica; Sung, Yongjin; Dao, Ming; Lim, Chwee Teck; Preiser, Peter Rainer; Suresh, Subra

    2011-01-01

    Upon infection and development within human erythrocytes, P. falciparum induces alterations to the infected RBC morphology and bio-mechanical properties to eventually rupture the host cells through parasitic and host derived proteases of cysteine and serine families. We used previously reported broad-spectrum inhibitors (E64d, EGTA-AM and chymostatin) to inhibit these proteases and impede rupture to analyze mechanical signatures associated with parasite escape. Treatment of late-stage iRBCs with E64d and EGTA-AM prevented rupture, resulted in no major RBC cytoskeletal reconfiguration but altered schizont morphology followed by dramatic re-distribution of three-dimensional refractive index (3D-RI) within the iRBC. These phenotypes demonstrated several-fold increased iRBC membrane flickering. In contrast, chymostatin treatment showed no 3D-RI changes and caused elevated fluctuations solely within the parasitophorous vacuole. We show that E64d and EGTA-AM supported PV breakdown and the resulting elevated fluctuations followed non-Gaussian pattern that resulted from direct merozoite impingement against the iRBC membrane. Optical trapping experiments highlighted reduced deformability of the iRBC membranes upon rupture-arrest, more specifically in the treatments that facilitated PV breakdown. Taken together, our experiments provide novel mechanistic interpretations on the role of parasitophorous vacuole in maintaining the spherical schizont morphology, the impact of PV breakdown on iRBC membrane fluctuations leading to eventual parasite escape and the evolution of membrane stiffness properties of host cells in which merozoites were irreversibly trapped, recourse to protease inhibitors. These findings provide a comprehensive, previously unavailable, body of information on the combined effects of biochemical and biophysical factors on parasite egress from iRBCs.

  10. Biophysical pathology in cancer transformation

    Czech Academy of Sciences Publication Activity Database

    Pokorný, Jiří; Pokorný, Jan

    S1, Nov (2013), s. 1-9 ISSN 2324-9110 R&D Projects: GA ČR(CZ) GAP102/11/0649 Institutional support: RVO:68378271 ; RVO:67985882 Keywords : cancer biophysics * Warburg effect * reverse Warburg effect * biological electrodynamics * coherent states Subject RIV: BO - Biophysics

  11. Biophysical Neural Spiking, Bursting, and Excitability Dynamics in Reconfigurable Analog VLSI.

    Science.gov (United States)

    Yu, T; Sejnowski, T J; Cauwenberghs, G

    2011-10-01

    We study a range of neural dynamics under variations in biophysical parameters underlying extended Morris-Lecar and Hodgkin-Huxley models in three gating variables. The extended models are implemented in NeuroDyn, a four neuron, twelve synapse continuous-time analog VLSI programmable neural emulation platform with generalized channel kinetics and biophysical membrane dynamics. The dynamics exhibit a wide range of time scales extending beyond 100 ms neglected in typical silicon models of tonic spiking neurons. Circuit simulations and measurements show transition from tonic spiking to tonic bursting dynamics through variation of a single conductance parameter governing calcium recovery. We similarly demonstrate transition from graded to all-or-none neural excitability in the onset of spiking dynamics through the variation of channel kinetic parameters governing the speed of potassium activation. Other combinations of variations in conductance and channel kinetic parameters give rise to phasic spiking and spike frequency adaptation dynamics. The NeuroDyn chip consumes 1.29 mW and occupies 3 mm × 3 mm in 0.5 μm CMOS, supporting emerging developments in neuromorphic silicon-neuron interfaces.

  12. C- and N-truncated antimicrobial peptides from LFampin 265 - 284: Biophysical versus microbiology results

    Directory of Open Access Journals (Sweden)

    Regina Adão

    2011-01-01

    Full Text Available Lactoferrin is a glycoprotein with two globular lobes, each having two domains. Since the discovery of its antimicrobial properties, efforts have been made to find peptides derived from this protein showing antimicrobial properties. Most peptides initially studied were derived from Lactoferricin B, obtained from the protein by digestion with pepsin. More recently, a new family of antimicrobial peptides (AMPs derived from Lactoferrin was discovered by Bolcher et al, and named Lactoferrampin (LFampin. The original sequence of LFampin contained residues 268 - 284 from the N1 domain of Lactoferrin. From this peptide, the Bolscher′s group synthesized a collection of peptides obtained by extension and / or truncation at the C or N-terminal sides, in order to unravel the main structural features responsible for antimicrobial action. Here, we present results for three of these peptides, namely LFampin 265 - 284, LFampin 265 - 280, and LFampin 270 - 284. The peptides were tested against bacteria (E. coli and S. sanguinis, fungi (C. albicans, and model membranes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC, 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol] (DMPG, and their mixtures at a ratio of 3 : 1 (DMPC : DMPG (3 : 1. The ability to adopt a helical conformation was followed by a circular dichroism (CD, and the perturbation of the gel to the liquid-crystalline phase transition of the membrane was characterized by differential scanning calorimetry (DSC. Distinct behavior was observed in the three peptides, both from the microbiology and model membrane studies, with the biophysical results showing excellent correlation with the microbiology activity studies. LFampin 265 - 284 was the most active peptide toward the tested microorganisms, and in the biophysical studies it showed the highest ability to form an a-helix and the strongest interaction with model membranes, followed by LFampin 265 - 280. LFampin 270 - 284 was inactive, showing

  13. Genotype-induced changes in biophysical properties of frontal cortex lipid raft from APP/PS1 transgenic mice

    Directory of Open Access Journals (Sweden)

    Mario L Diaz

    2012-11-01

    Full Text Available Alterations in the lipid composition of lipid rafts have been demonstrated both in human brain and transgenic mouse models, and it has been postulated that aberrant lipid composition in lipid rafts is partly responsible for neuronal degeneration. In order to assess the impact of lipid changes on lipid raft functional properties, we have aimed at determining relevant physicochemical modifications in lipid rafts purified from frontal cortex of wild type (WT and APP/PS1 double transgenic mice. By means of steady-state fluorescence anisotropy analyses using two lipid soluble fluorescent probes, TMA-DPH (1-[(4-trimethyl-aminophenyl]-6-phenyl-1,3,5-hexatriene and DPH (1,6-diphenyl-1,3,5-hexatriene, we demonstrate that cortical lipid rafts from WT and APP/PS1 animals exhibit different biophysical behaviours, depending on genotype but also on age. Thus, aged APP/PS1 animals exhibited slightly more liquid-ordered lipid rafts than WT counterparts. Membrane microviscosity napp analyses demonstrate that WT lipid rafts are more fluid than APP/PS1 animals of similar age, both at the aqueous interface and hydrophobic core of the membrane. napp in APP/PS1 animals was higher for DPH than for TMA-DPH under similar experimental conditions, indicating that the internal core of the membrane is more viscous than the raft membrane at the aqueous interface. The most dramatic changes in biophysical properties of lipid rafts were observed when membrane cholesterol was depleted with methyl-beta-cyclodextrin. Overall, our results indicate that APP/PS1 genotype strongly affects physicochemical properties of lipid raft. Such alterations appear not to be homogeneous across the raft membrane axis, but rather are more prominent at the membrane plane. These changes correlate with aberrant proportions of sphingomyelin, cholesterol and saturated fatty acids, as well as polyunsaturated fatty acids, measured in lipid rafts from frontal cortex in this familial model of

  14. Assimilation of Biophysical Neuronal Dynamics in Neuromorphic VLSI.

    Science.gov (United States)

    Wang, Jun; Breen, Daniel; Akinin, Abraham; Broccard, Frederic; Abarbanel, Henry D I; Cauwenberghs, Gert

    2017-12-01

    Representing the biophysics of neuronal dynamics and behavior offers a principled analysis-by-synthesis approach toward understanding mechanisms of nervous system functions. We report on a set of procedures assimilating and emulating neurobiological data on a neuromorphic very large scale integrated (VLSI) circuit. The analog VLSI chip, NeuroDyn, features 384 digitally programmable parameters specifying for 4 generalized Hodgkin-Huxley neurons coupled through 12 conductance-based chemical synapses. The parameters also describe reversal potentials, maximal conductances, and spline regressed kinetic functions for ion channel gating variables. In one set of experiments, we assimilated membrane potential recorded from one of the neurons on the chip to the model structure upon which NeuroDyn was designed using the known current input sequence. We arrived at the programmed parameters except for model errors due to analog imperfections in the chip fabrication. In a related set of experiments, we replicated songbird individual neuron dynamics on NeuroDyn by estimating and configuring parameters extracted using data assimilation from intracellular neural recordings. Faithful emulation of detailed biophysical neural dynamics will enable the use of NeuroDyn as a tool to probe electrical and molecular properties of functional neural circuits. Neuroscience applications include studying the relationship between molecular properties of neurons and the emergence of different spike patterns or different brain behaviors. Clinical applications include studying and predicting effects of neuromodulators or neurodegenerative diseases on ion channel kinetics.

  15. Membrane fluidization by alcohols inhibits DesK-DesR signalling in Bacillus subtilis.

    Science.gov (United States)

    Vaňousová, Kateřina; Beranová, Jana; Fišer, Radovan; Jemioła-Rzemińska, Malgorzata; Matyska Lišková, Petra; Cybulski, Larisa; Strzałka, Kazimierz; Konopásek, Ivo

    2018-03-01

    After cold shock, the Bacillus subtilis desaturase Des introduces double bonds into the fatty acids of existing membrane phospholipids. The synthesis of Des is regulated exclusively by the two-component system DesK/DesR; DesK serves as a sensor of the state of the membrane and triggers Des synthesis after a decrease in membrane fluidity. The aim of our work is to investigate the biophysical changes in the membrane that are able to affect the DesK signalling state. Using linear alcohols (ethanol, propanol, butanol, hexanol, octanol) and benzyl alcohol, we were able to suppress Des synthesis after a temperature downshift. The changes in the biophysical properties of the membrane caused by alcohol addition were followed using membrane fluorescent probes and differential scanning calorimetry. We found that the membrane fluidization induced by alcohols was reflected in an increased hydration at the lipid-water interface. This is associated with a decrease in DesK activity. The addition of alcohol mimics a temperature increase, which can be measured isothermically by fluorescence anisotropy. The effect of alcohols on the membrane periphery is in line with the concept of the mechanism by which two hydrophilic motifs located at opposite ends of the transmembrane region of DesK, which work as a molecular caliper, sense temperature-dependent variations in membrane properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Deciphering the BAR code of membrane modulators.

    Science.gov (United States)

    Salzer, Ulrich; Kostan, Julius; Djinović-Carugo, Kristina

    2017-07-01

    The BAR domain is the eponymous domain of the "BAR-domain protein superfamily", a large and diverse set of mostly multi-domain proteins that play eminent roles at the membrane cytoskeleton interface. BAR domain homodimers are the functional units that peripherally associate with lipid membranes and are involved in membrane sculpting activities. Differences in their intrinsic curvatures and lipid-binding properties account for a large variety in membrane modulating properties. Membrane activities of BAR domains are further modified and regulated by intramolecular or inter-subunit domains, by intermolecular protein interactions, and by posttranslational modifications. Rather than providing detailed cell biological information on single members of this superfamily, this review focuses on biochemical, biophysical, and structural aspects and on recent findings that paradigmatically promote our understanding of processes driven and modulated by BAR domains.

  17. G protein-membrane interactions II: Effect of G protein-linked lipids on membrane structure and G protein-membrane interactions.

    Science.gov (United States)

    Casas, Jesús; Ibarguren, Maitane; Álvarez, Rafael; Terés, Silvia; Lladó, Victoria; Piotto, Stefano P; Concilio, Simona; Busquets, Xavier; López, David J; Escribá, Pablo V

    2017-09-01

    G proteins often bear myristoyl, palmitoyl and isoprenyl moieties, which favor their association with the membrane and their accumulation in G Protein Coupled Receptor-rich microdomains. These lipids influence the biophysical properties of membranes and thereby modulate G protein binding to bilayers. In this context, we showed here that geranylgeraniol, but neither myristate nor palmitate, increased the inverted hexagonal (H II ) phase propensity of phosphatidylethanolamine-containing membranes. While myristate and palmitate preferentially associated with phosphatidylcholine membranes, geranylgeraniol favored nonlamellar-prone membranes. In addition, Gαi 1 monomers had a higher affinity for lamellar phases, while Gβγ and Gαβγ showed a marked preference for nonlamellar prone membranes. Moreover, geranylgeraniol enhanced the binding of G protein dimers and trimers to phosphatidylethanolamine-containing membranes, yet it decreased that of monomers. By contrast, both myristate and palmitate increased the Gαi 1 preference for lamellar membranes. Palmitoylation reinforced the binding of the monomer to PC membranes and myristoylation decreased its binding to PE-enriched bilayer. Finally, binding of dimers and trimers to lamellar-prone membranes was decreased by palmitate and myristate, but it was increased in nonlamellar-prone bilayers. These results demonstrate that co/post-translational G protein lipid modifications regulate the membrane lipid structure and that they influence the physico-chemical properties of membranes, which in part explains why G protein subunits sort to different plasma membrane domains. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Bioelectrochemistry II membrane phenomena

    CERN Document Server

    Blank, M

    1987-01-01

    This book contains the lectures of the second course devoted to bioelectro­ chemistry, held within the framework of the International School of Biophysics. In this course another very large field of bioelectrochemistry, i. e. the field of Membrane Phenomena, was considered, which itself consists of several different, but yet related subfields. Here again, it can be easily stated that it is impossible to give a complete and detailed picture of all membrane phenomena of biological interest in a short course of about one and half week. Therefore the same philosophy, as the one of the first course, was followed, to select a series of lectures at postgraduate level, giving a synthesis of several membrane phenomena chosen among the most'important ones. These lectures should show the large variety of membrane-regulated events occurring in living bodies, and serve as sound interdisciplinary basis to start a special­ ized study of biological phenomena, for which the investigation using the dual approach, physico-che...

  19. Biophysical applications of satellite remote sensing

    CERN Document Server

    Hanes, Jonathan

    2014-01-01

    Including an introduction and historical overview of the field, this comprehensive synthesis of the major biophysical applications of satellite remote sensing includes in-depth discussion of satellite-sourced biophysical metrics such as leaf area index.

  20. Structure and physical properties of bio membranes and model membranes

    International Nuclear Information System (INIS)

    Tibor Hianik

    2006-01-01

    Bio membranes belong to the most important structures of the cell and the cell organelles. They play not only structural role of the barrier separating the external and internal part of the membrane but contain also various functional molecules, like receptors, ionic channels, carriers and enzymes. The cell membrane also preserves non-equilibrium state in a cell which is crucial for maintaining its excitability and other signaling functions. The growing interest to the bio membranes is also due to their unique physical properties. From physical point of view the bio membranes, that are composed of lipid bilayer into which are incorporated integral proteins and on their surface are anchored peripheral proteins and polysaccharides, represent liquid s crystal of smectic type. The bio membranes are characterized by anisotropy of structural and physical properties. The complex structure of bio membranes makes the study of their physical properties rather difficult. Therefore several model systems that mimic the structure of bio membranes were developed. Among them the lipid monolayers at an air-water interphase, bilayer lipid membranes, supported bilayer lipid membranes and liposomes are most known. This work is focused on the introduction into the physical word of the bio membranes and their models. After introduction to the membrane structure and the history of its establishment, the physical properties of the bio membranes and their models are stepwise presented. The most focus is on the properties of lipid monolayers, bilayer lipid membranes, supported bilayer lipid membranes and liposomes that were most detailed studied. This lecture has tutorial character that may be useful for undergraduate and graduate students in the area of biophysics, biochemistry, molecular biology and bioengineering, however it contains also original work of the author and his co-worker and PhD students, that may be useful also for specialists working in the field of bio membranes and model

  1. Historical and Critical Review on Biophysical Economics

    Science.gov (United States)

    Adigüzel, Yekbun

    2016-07-01

    Biophysical economics is initiated with the long history of the relation of economics with ecological basis and biophysical perspectives of the physiocrats. It inherently has social, economic, biological, environmental, natural, physical, and scientific grounds. Biological entities in economy like the resources, consumers, populations, and parts of production systems, etc. could all be dealt by biophysical economics. Considering this wide scope, current work is a “biophysical economics at a glance” rather than a comprehensive review of the full range of topics that may just be adequately covered in a book-length work. However, the sense of its wide range of applications is aimed to be provided to the reader in this work. Here, modern approaches and biophysical growth theory are presented after the long history and an overview of the concepts in biophysical economics. Examples of the recent studies are provided at the end with discussions. This review is also related to the work by Cleveland, “Biophysical Economics: From Physiocracy to Ecological Economics and Industrial Ecology” [C. J. Cleveland, in Advances in Bioeconomics and Sustainability: Essay in Honor of Nicholas Gerogescu-Roegen, eds. J. Gowdy and K. Mayumi (Edward Elgar Publishing, Cheltenham, England, 1999), pp. 125-154.]. Relevant parts include critics and comments on the presented concepts in a parallelized fashion with the Cleveland’s work.

  2. Biophysical mechanisms complementing "classical" cell biology.

    Science.gov (United States)

    Funk, Richard H W

    2018-01-01

    This overview addresses phenomena in cell- and molecular biology which are puzzling by their fast and highly coordinated way of organization. Generally, it appears that informative processes probably involved are more on the biophysical than on the classical biochemical side. The coordination problem is explained within the first part of the review by the topic of endogenous electrical phenomena. These are found e.g. in fast tissue organization and reorganization processes like development, wound healing and regeneration. Here, coupling into classical biochemical signaling and reactions can be shown by modern microscopy, electronics and bioinformatics. Further, one can follow the triggered reactions seamlessly via molecular biology till into genetics. Direct observation of intracellular electric processes is very difficult because of e.g. shielding through the cell membrane and damping by other structures. Therefore, we have to rely on photonic and photon - phonon coupling phenomena like molecular vibrations, which are addressed within the second part. Molecules normally possess different charge moieties and thus small electromagnetic (EMF) patterns arise during molecular vibration. These patterns can now be measured best within the optical part of the spectrum - much less in the lower terahertz till kHz and lower Hz part (third part of this review). Finally, EMFs facilitate quantum informative processes in coherent domains of molecular, charge and electron spin motion. This helps to coordinate such manifold and intertwined processes going on within cells, tissues and organs (part 4). Because the phenomena described in part 3 and 4 of the review still await really hard proofs we need concerted efforts and a combination of biophysics, molecular biology and informatics to unravel the described mysteries in "physics of life".

  3. Layer-by-layer cell membrane assembly

    Science.gov (United States)

    Matosevic, Sandro; Paegel, Brian M.

    2013-11-01

    Eukaryotic subcellular membrane systems, such as the nuclear envelope or endoplasmic reticulum, present a rich array of architecturally and compositionally complex supramolecular targets that are as yet inaccessible. Here we describe layer-by-layer phospholipid membrane assembly on microfluidic droplets, a route to structures with defined compositional asymmetry and lamellarity. Starting with phospholipid-stabilized water-in-oil droplets trapped in a static droplet array, lipid monolayer deposition proceeds as oil/water-phase boundaries pass over the droplets. Unilamellar vesicles assembled layer-by-layer support functional insertion both of purified and of in situ expressed membrane proteins. Synthesis and chemical probing of asymmetric unilamellar and double-bilayer vesicles demonstrate the programmability of both membrane lamellarity and lipid-leaflet composition during assembly. The immobilized vesicle arrays are a pragmatic experimental platform for biophysical studies of membranes and their associated proteins, particularly complexes that assemble and function in multilamellar contexts in vivo.

  4. Quality Saving Mechanisms of Mitochondria during Aging in a Fully Time-Dependent Computational Biophysical Model.

    Directory of Open Access Journals (Sweden)

    Daniel Mellem

    Full Text Available Mitochondria are essential for the energy production of eukaryotic cells. During aging mitochondria run through various processes which change their quality in terms of activity, health and metabolic supply. In recent years, many of these processes such as fission and fusion of mitochondria, mitophagy, mitochondrial biogenesis and energy consumption have been subject of research. Based on numerous experimental insights, it was possible to qualify mitochondrial behaviour in computational simulations. Here, we present a new biophysical model based on the approach of Figge et al. in 2012. We introduce exponential decay and growth laws for each mitochondrial process to derive its time-dependent probability during the aging of cells. All mitochondrial processes of the original model are mathematically and biophysically redefined and additional processes are implemented: Mitochondrial fission and fusion is separated into a metabolic outer-membrane part and a protein-related inner-membrane part, a quality-dependent threshold for mitophagy and mitochondrial biogenesis is introduced and processes for activity-dependent internal oxidative stress as well as mitochondrial repair mechanisms are newly included. Our findings reveal a decrease of mitochondrial quality and a fragmentation of the mitochondrial network during aging. Additionally, the model discloses a quality increasing mechanism due to the interplay of the mitophagy and biogenesis cycle and the fission and fusion cycle of mitochondria. It is revealed that decreased mitochondrial repair can be a quality saving process in aged cells. Furthermore, the model finds strategies to sustain the quality of the mitochondrial network in cells with high production rates of reactive oxygen species due to large energy demands. Hence, the model adds new insights to biophysical mechanisms of mitochondrial aging and provides novel understandings of the interdependency of mitochondrial processes.

  5. How membrane lipids control the 3D structure and function of receptors

    OpenAIRE

    Jacques Fantini; Francisco J. Barrantes

    2018-01-01

    The cohabitation of lipids and proteins in the plasma membrane of mammalian cells is controlled by specific biochemical and biophysical rules. Lipids may be either constitutively tightly bound to cell-surface receptors (non-annular lipids) or less tightly attached to the external surface of the protein (annular lipids). The latter are exchangeable with surrounding bulk membrane lipids on a faster time scale than that of non-annular lipids. Not only do non-annular lipids bind to membrane prote...

  6. Effect of Plasma Membrane Semipermeability in Making the Membrane Electric Double Layer Capacitances Significant.

    Science.gov (United States)

    Sinha, Shayandev; Sachar, Harnoor Singh; Das, Siddhartha

    2018-01-30

    Electric double layers (or EDLs) formed at the membrane-electrolyte interface (MEI) and membrane-cytosol interface (MCI) of a charged lipid bilayer plasma membrane develop finitely large capacitances. However, these EDL capacitances are often much larger than the intrinsic capacitance of the membrane, and all of these capacitances are in series. Consequently, the effect of these EDL capacitances in dictating the overall membrane-EDL effective capacitance C eff becomes negligible. In this paper, we challenge this conventional notion pertaining to the membrane-EDL capacitances. We demonstrate that, on the basis of the system parameters, the EDL capacitance for both the permeable and semipermeable membranes can be small enough to influence C eff . For the semipermeable membranes, however, this lowering of the EDL capacitance can be much larger, ensuring a reduction of C eff by more than 20-25%. Furthermore, for the semipermeable membranes, the reduction in C eff is witnessed over a much larger range of system parameters. We attribute such an occurrence to the highly nonintuitive electrostatic potential distribution associated with the recently discovered phenomena of charge-inversion-like electrostatics and the attainment of a positive zeta potential at the MCI for charged semipermeable membranes. We anticipate that our findings will impact the quantification and the identification of a large number of biophysical phenomena that are probed by measuring the plasma membrane capacitance.

  7. ECClipids17: adapting atomistic lipid models to correct cation-membrane interactions

    Czech Academy of Sciences Publication Activity Database

    Melcr, Josef; Ollila, Samuli; Baxová, Katarína; Jungwirth, Pavel; Martinez-Seara, Hector

    2017-01-01

    Roč. 46, Suppl 1 (2017), S224 ISSN 0175-7571. [IUPAB congress /19./ and EBSA congress /11./. 16.07.2017-20.07.2017, Edinburgh] Institutional support: RVO:61388963 Keywords : ECC * membrane interactions Subject RIV: BO - Biophysics

  8. Cell-free expressed bacteriorhodopsin in different soluble membrane mimetics: biophysical properties and NMR accessibility.

    Science.gov (United States)

    Etzkorn, Manuel; Raschle, Thomas; Hagn, Franz; Gelev, Vladimir; Rice, Amanda J; Walz, Thomas; Wagner, Gerhard

    2013-03-05

    Selecting a suitable membrane-mimicking environment is of fundamental importance for the investigation of membrane proteins. Nonconventional surfactants, such as amphipathic polymers (amphipols) and lipid bilayer nanodiscs, have been introduced as promising environments that may overcome intrinsic disadvantages of detergent micelle systems. However, structural insights into the effects of different environments on the embedded protein are limited. Here, we present a comparative study of the heptahelical membrane protein bacteriorhodopsin in detergent micelles, amphipols, and nanodiscs. Our results confirm that nonconventional environments can increase stability of functional bacteriorhodopsin, and demonstrate that well-folded heptahelical membrane proteins are, in principle, accessible by solution-NMR methods in amphipols and phospholipid nanodiscs. Our data distinguish regions of bacteriorhodopsin that mediate membrane/solvent contacts in the tested environments, whereas the protein's functional inner core remains almost unperturbed. The presented data allow comparing the investigated membrane mimetics in terms of NMR spectral quality and thermal stability required for structural studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Theoretical Molecular Biophysics

    CERN Document Server

    Scherer, Philipp

    2010-01-01

    "Theoretical Molecular Biophysics" is an advanced study book for students, shortly before or after completing undergraduate studies, in physics, chemistry or biology. It provides the tools for an understanding of elementary processes in biology, such as photosynthesis on a molecular level. A basic knowledge in mechanics, electrostatics, quantum theory and statistical physics is desirable. The reader will be exposed to basic concepts in modern biophysics such as entropic forces, phase separation, potentials of mean force, proton and electron transfer, heterogeneous reactions coherent and incoherent energy transfer as well as molecular motors. Basic concepts such as phase transitions of biopolymers, electrostatics, protonation equilibria, ion transport, radiationless transitions as well as energy- and electron transfer are discussed within the frame of simple models.

  10. Biophysics an introduction

    CERN Document Server

    Cotteril, Rodney

    2002-01-01

    Biophysics: An Introduction, is a concise balanced introduction to this subject. Written in an accessible and readable style, the book takes a fresh, modern approach with the author successfully combining key concepts and theory with relevant applications and examples drawn from the field as a whole. Beginning with a brief introduction to the origins of biophysics, the book takes the reader through successive levels of complexity, from atoms to molecules, structures, systems and ultimately to the behaviour of organisms. The book also includes extensive coverage of biopolymers, biomembranes, biological energy, and nervous systems. The text not only explores basic ideas, but also discusses recent developments, such as protein folding, DNA/RNA conformations, molecular motors, optical tweezers and the biological origins of consciousness and intelligence.

  11. Biomechanics and Thermodynamics of Nanoparticle Interactions with Plasma and Endosomal Membrane Lipids in Cellular Uptake and Endosomal Escape

    Science.gov (United States)

    2015-01-01

    To be effective for cytoplasmic delivery of therapeutics, nanoparticles (NPs) taken up via endocytic pathways must efficiently transport across the cell membrane and subsequently escape from the secondary endosomes. We hypothesized that the biomechanical and thermodynamic interactions of NPs with plasma and endosomal membrane lipids are involved in these processes. Using model plasma and endosomal lipid membranes, we compared the interactions of cationic NPs composed of poly(d,l-lactide-co-glycolide) modified with the dichain surfactant didodecyldimethylammonium bromide (DMAB) or the single-chain surfactant cetyltrimethylammonium bromide (CTAB) vs anionic unmodified NPs of similar size. We validated our hypothesis in doxorubicin-sensitive (MCF-7, with relatively fluid membranes) and resistant breast cancer cells (MCF-7/ADR, with rigid membranes). Despite their cationic surface charges, DMAB- and CTAB-modified NPs showed different patterns of biophysical interaction: DMAB-modified NPs induced bending of the model plasma membrane, whereas CTAB-modified NPs condensed the membrane, thereby resisted bending. Unmodified NPs showed no effects on bending. DMAB-modified NPs also induced thermodynamic instability of the model endosomal membrane, whereas CTAB-modified and unmodified NPs had no effect. Since bending of the plasma membrane and destabilization of the endosomal membrane are critical biophysical processes in NP cellular uptake and endosomal escape, respectively, we tested these NPs for cellular uptake and drug efficacy. Confocal imaging showed that in both sensitive and resistant cells DMAB-modified NPs exhibited greater cellular uptake and escape from endosomes than CTAB-modified or unmodified NPs. Further, paclitaxel-loaded DMAB-modified NPs induced greater cytotoxicity even in resistant cells than CTAB-modified or unmodified NPs or drug in solution, demonstrating the potential of DMAB-modified NPs to overcome the transport barrier in resistant cells. In

  12. Exploiting lipopolysaccharide-induced deformation of lipid bilayers to modify membrane composition and generate two-dimensional geometric membrane array patterns

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Peter G. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Swingle, Kirstie L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States); Paxton, Walter F. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Nogan, John J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Stromberg, Loreen R. [Univ. of New Mexico, Albuquerque, NM (United States); Firestone, Millicent A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mukundan, Harshini [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); New Mexico Consortium, Los Alamos, NM (United States); Montaño, Gabriel A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-05-27

    Supported lipid bilayers have proven effective as model membranes for investigating biophysical processes and in development of sensor and array technologies. The ability to modify lipid bilayers after their formation and in situ could greatly advance membrane technologies, but is difficult via current state-of-the-art technologies. Here we demonstrate a novel method that allows the controlled post-formation processing and modification of complex supported lipid bilayer arrangements, under aqueous conditions. We exploit the destabilization effect of lipopolysaccharide, an amphiphilic biomolecule, interacting with lipid bilayers to generate voids that can be backfilled to introduce desired membrane components. We further demonstrate that when used in combination with a single, traditional soft lithography process, it is possible to generate hierarchically-organized membrane domains and microscale 2-D array patterns of domains. Significantly, this technique can be used to repeatedly modify membranes allowing iterative control over membrane composition. This approach expands our toolkit for functional membrane design, with potential applications for enhanced materials templating, biosensing and investigating lipid-membrane processes.

  13. Reconstitution of the anti-apoptotic Bcl-2 protein into lipid membranes and biophysical evidence for its detergent-driven association with the pro-apoptotic Bax protein.

    Directory of Open Access Journals (Sweden)

    Marcus Wallgren

    Full Text Available The anti-apoptotic B-cell CLL/lymphoma-2 (Bcl-2 protein and its counterpart, the pro-apoptotic Bcl-2-associated X protein (Bax, are key players in the regulation of the mitochondrial pathway of apoptosis. However, how they interact at the mitochondrial outer membrane (MOM and there determine whether the cell will live or be sentenced to death remains unknown. Competing models have been presented that describe how Bcl-2 inhibits the cell-killing activity of Bax, which is common in treatment-resistant tumors where Bcl-2 is overexpressed. Some studies suggest that Bcl-2 binds directly to and sequesters Bax, while others suggest an indirect process whereby Bcl-2 blocks BH3-only proteins and prevents them from activating Bax. Here we present the results of a biophysical study in which we investigated the putative interaction of solubilized full-length human Bcl-2 with Bax and the scope for incorporating the former into a native-like lipid environment. Far-UV circular dichroism (CD spectroscopy was used to detect direct Bcl-2-Bax-interactions in the presence of polyoxyethylene-(23-lauryl-ether (Brij-35 detergent at a level below its critical micelle concentration (CMC. Additional surface plasmon resonance (SPR measurements confirmed this observation and revealed a high affinity between the Bax and Bcl-2 proteins. Upon formation of this protein-protein complex, Bax also prevented the binding of antimycin A2 (a known inhibitory ligand of Bcl-2 to the Bcl-2 protein, as fluorescence spectroscopy experiments showed. In addition, Bcl-2 was able to form mixed micelles with Triton X-100 solubilized neutral phospholipids in the presence of high concentrations of Brij-35 (above its CMC. Following detergent removal, the integral membrane protein was found to have been fully reconstituted into a native-like membrane environment, as confirmed by ultracentrifugation and subsequent SDS-PAGE experiments.

  14. DNA hybridization on membrane-modified carbon electrodes

    Czech Academy of Sciences Publication Activity Database

    Kouřilová, Alena; Babkina, S. S.; Cahová, Kateřina; Havran, Luděk; Jelen, František; Paleček, Emil; Fojta, Miroslav

    2005-01-01

    Roč. 38, - (2005), s. 2493-2507 ISSN 0003-2719 R&D Projects: GA MPO(CZ) 1H-PK/42; GA AV ČR(CZ) IAA4004402; GA AV ČR(CZ) IBS5004355 Institutional research plan: CEZ:AV0Z50040507 Keywords : DNA hybridization * electrochemical DNA sensor * nitrocellulose membrane Subject RIV: BO - Biophysics Impact factor: 1.036, year: 2005

  15. Interferometric scattering (iSCAT) microscopy: studies of biological membrane dynamics

    Science.gov (United States)

    Reina, Francesco; Galiani, Silvia; Shrestha, Dilip; Sezgin, Erdinc; Lagerholm, B. Christoffer; Cole, Daniel; Kukura, Philipp; Eggeling, Christian

    2018-02-01

    The study of the organization and dynamics of molecules in model and cellular membranes is an important topic in contemporary biophysics. Imaging and single particle tracking in this particular field, however, proves particularly demanding, as it requires simultaneously high spatio-temporal resolution and high signal-to-noise ratios. A remedy to this challenge might be Interferometric Scattering (iSCAT) microscopy, due to its fast sampling rates, label-free imaging capabilities and, most importantly, tuneable signal level output. Here we report our recent advances in the imaging and molecular tracking on phase-separated model membrane systems and live-cell membranes using this technique.

  16. Energy efficient neural stimulation: coupling circuit design and membrane biophysics.

    Science.gov (United States)

    Foutz, Thomas J; Ackermann, D Michael; Kilgore, Kevin L; McIntyre, Cameron C

    2012-01-01

    The delivery of therapeutic levels of electrical current to neural tissue is a well-established treatment for numerous indications such as Parkinson's disease and chronic pain. While the neuromodulation medical device industry has experienced steady clinical growth over the last two decades, much of the core technology underlying implanted pulse generators remain unchanged. In this study we propose some new methods for achieving increased energy-efficiency during neural stimulation. The first method exploits the biophysical features of excitable tissue through the use of a centered-triangular stimulation waveform. Neural activation with this waveform is achieved with a statistically significant reduction in energy compared to traditional rectangular waveforms. The second method demonstrates energy savings that could be achieved by advanced circuitry design. We show that the traditional practice of using a fixed compliance voltage for constant-current stimulation results in substantial energy loss. A portion of this energy can be recuperated by adjusting the compliance voltage to real-time requirements. Lastly, we demonstrate the potential impact of axon fiber diameter on defining the energy-optimal pulse-width for stimulation. When designing implantable pulse generators for energy efficiency, we propose that the future combination of a variable compliance system, a centered-triangular stimulus waveform, and an axon diameter specific stimulation pulse-width has great potential to reduce energy consumption and prolong battery life in neuromodulation devices.

  17. Energy efficient neural stimulation: coupling circuit design and membrane biophysics.

    Directory of Open Access Journals (Sweden)

    Thomas J Foutz

    Full Text Available The delivery of therapeutic levels of electrical current to neural tissue is a well-established treatment for numerous indications such as Parkinson's disease and chronic pain. While the neuromodulation medical device industry has experienced steady clinical growth over the last two decades, much of the core technology underlying implanted pulse generators remain unchanged. In this study we propose some new methods for achieving increased energy-efficiency during neural stimulation. The first method exploits the biophysical features of excitable tissue through the use of a centered-triangular stimulation waveform. Neural activation with this waveform is achieved with a statistically significant reduction in energy compared to traditional rectangular waveforms. The second method demonstrates energy savings that could be achieved by advanced circuitry design. We show that the traditional practice of using a fixed compliance voltage for constant-current stimulation results in substantial energy loss. A portion of this energy can be recuperated by adjusting the compliance voltage to real-time requirements. Lastly, we demonstrate the potential impact of axon fiber diameter on defining the energy-optimal pulse-width for stimulation. When designing implantable pulse generators for energy efficiency, we propose that the future combination of a variable compliance system, a centered-triangular stimulus waveform, and an axon diameter specific stimulation pulse-width has great potential to reduce energy consumption and prolong battery life in neuromodulation devices.

  18. An allosteric gating model recapitulates the biophysical properties of IK,L expressed in mouse vestibular type I hair cells.

    Science.gov (United States)

    Spaiardi, Paolo; Tavazzani, Elisa; Manca, Marco; Milesi, Veronica; Russo, Giancarlo; Prigioni, Ivo; Marcotti, Walter; Magistretti, Jacopo; Masetto, Sergio

    2017-11-01

    Vestibular type I and type II hair cells and their afferent fibres send information to the brain regarding the position and movement of the head. The characteristic feature of type I hair cells is the expression of a low-voltage-activated outward rectifying K + current, I K,L , whose biophysical properties and molecular identity are still largely unknown. In vitro, the afferent nerve calyx surrounding type I hair cells causes unstable intercellular K + concentrations, altering the biophysical properties of I K,L . We found that in the absence of the calyx, I K,L in type I hair cells exhibited unique biophysical activation properties, which were faithfully reproduced by an allosteric channel gating scheme. These results form the basis for a molecular and pharmacological identification of I K,L . Type I and type II hair cells are the sensory receptors of the mammalian vestibular epithelia. Type I hair cells are characterized by their basolateral membrane being enveloped in a single large afferent nerve terminal, named the calyx, and by the expression of a low-voltage-activated outward rectifying K + current, I K,L . The biophysical properties and molecular profile of I K,L are still largely unknown. By using the patch-clamp whole-cell technique, we examined the voltage- and time-dependent properties of I K,L in type I hair cells of the mouse semicircular canal. We found that the biophysical properties of I K,L were affected by an unstable K + equilibrium potential (V eq K + ). Both the outward and inward K + currents shifted V eq K + consistent with K + accumulation or depletion, respectively, in the extracellular space, which we attributed to a residual calyx attached to the basolateral membrane of the hair cells. We therefore optimized the hair cell dissociation protocol in order to isolate mature type I hair cells without their calyx. In these cells, the uncontaminated I K,L showed a half-activation at -79.6 mV and a steep voltage dependence (2.8 mV). I K,L also

  19. Anionic lipids and the maintenance of membrane electrostatics in eukaryotes.

    Science.gov (United States)

    Platre, Matthieu Pierre; Jaillais, Yvon

    2017-02-01

    A wide range of signaling processes occurs at the cell surface through the reversible association of proteins from the cytosol to the plasma membrane. Some low abundant lipids are enriched at the membrane of specific compartments and thereby contribute to the identity of cell organelles by acting as biochemical landmarks. Lipids also influence membrane biophysical properties, which emerge as an important feature in specifying cellular territories. Such parameters are crucial for signal transduction and include lipid packing, membrane curvature and electrostatics. In particular, membrane electrostatics specifies the identity of the plasma membrane inner leaflet. Membrane surface charges are carried by anionic phospholipids, however the exact nature of the lipid(s) that powers the plasma membrane electrostatic field varies among eukaryotes and has been hotly debated during the last decade. Herein, we discuss the role of anionic lipids in setting up plasma membrane electrostatics and we compare similarities and differences that were found in different eukaryotic cells.

  20. Membrane remodeling by amyloidogenic and non-amyloidogenic proteins studied by EPR.

    Science.gov (United States)

    Varkey, Jobin; Langen, Ralf

    2017-07-01

    The advancement in site-directed spin labeling of proteins has enabled EPR studies to expand into newer research areas within the umbrella of protein-membrane interactions. Recently, membrane remodeling by amyloidogenic and non-amyloidogenic proteins has gained a substantial interest in relation to driving and controlling vital cellular processes such as endocytosis, exocytosis, shaping of organelles like endoplasmic reticulum, Golgi and mitochondria, intracellular vesicular trafficking, formation of filopedia and multivesicular bodies, mitochondrial fusion and fission, and synaptic vesicle fusion and recycling in neurotransmission. Misregulation in any of these processes due to an aberrant protein (mutation or misfolding) or alteration of lipid metabolism can be detrimental to the cell and cause disease. Dissection of the structural basis of membrane remodeling by proteins is thus quite necessary for an understanding of the underlying mechanisms, but it remains a formidable task due to the difficulties of various common biophysical tools in monitoring the dynamic process of membrane binding and bending by proteins. This is largely since membranes generally complicate protein structure analysis and this problem is amplified for structural analysis in the presence of different types of membrane curvatures. Recent EPR studies on membrane remodeling by proteins show that a significant structural information can be generated to delineate the role of different protein modules, domains and individual amino acids in the generation of membrane curvature. These studies also show how EPR can complement the data obtained by high resolution techniques such as X-ray and NMR. This perspective covers the application of EPR in recent studies for understanding membrane remodeling by amyloidogenic and non-amyloidogenic proteins that is useful for researchers interested in using or complimenting EPR to gain better understanding of membrane remodeling. We also discuss how a single

  1. Membrane remodeling by amyloidogenic and non-amyloidogenic proteins studied by EPR

    Science.gov (United States)

    Varkey, Jobin; Langen, Ralf

    2017-07-01

    The advancement in site-directed spin labeling of proteins has enabled EPR studies to expand into newer research areas within the umbrella of protein-membrane interactions. Recently, membrane remodeling by amyloidogenic and non-amyloidogenic proteins has gained a substantial interest in relation to driving and controlling vital cellular processes such as endocytosis, exocytosis, shaping of organelles like endoplasmic reticulum, Golgi and mitochondria, intracellular vesicular trafficking, formation of filopedia and multivesicular bodies, mitochondrial fusion and fission, and synaptic vesicle fusion and recycling in neurotransmission. Misregulation in any of these processes due to an aberrant protein (mutation or misfolding) or alteration of lipid metabolism can be detrimental to the cell and cause disease. Dissection of the structural basis of membrane remodeling by proteins is thus quite necessary for an understanding of the underlying mechanisms, but it remains a formidable task due to the difficulties of various common biophysical tools in monitoring the dynamic process of membrane binding and bending by proteins. This is largely since membranes generally complicate protein structure analysis and this problem is amplified for structural analysis in the presence of different types of membrane curvatures. Recent EPR studies on membrane remodeling by proteins show that a significant structural information can be generated to delineate the role of different protein modules, domains and individual amino acids in the generation of membrane curvature. These studies also show how EPR can complement the data obtained by high resolution techniques such as X-ray and NMR. This perspective covers the application of EPR in recent studies for understanding membrane remodeling by amyloidogenic and non-amyloidogenic proteins that is useful for researchers interested in using or complimenting EPR to gain better understanding of membrane remodeling. We also discuss how a single

  2. Kinetics and Thermodynamics of Membrane Protein Folding

    Directory of Open Access Journals (Sweden)

    Ernesto A. Roman

    2014-03-01

    Full Text Available Understanding protein folding has been one of the great challenges in biochemistry and molecular biophysics. Over the past 50 years, many thermodynamic and kinetic studies have been performed addressing the stability of globular proteins. In comparison, advances in the membrane protein folding field lag far behind. Although membrane proteins constitute about a third of the proteins encoded in known genomes, stability studies on membrane proteins have been impaired due to experimental limitations. Furthermore, no systematic experimental strategies are available for folding these biomolecules in vitro. Common denaturing agents such as chaotropes usually do not work on helical membrane proteins, and ionic detergents have been successful denaturants only in few cases. Refolding a membrane protein seems to be a craftsman work, which is relatively straightforward for transmembrane β-barrel proteins but challenging for α-helical membrane proteins. Additional complexities emerge in multidomain membrane proteins, data interpretation being one of the most critical. In this review, we will describe some recent efforts in understanding the folding mechanism of membrane proteins that have been reversibly refolded allowing both thermodynamic and kinetic analysis. This information will be discussed in the context of current paradigms in the protein folding field.

  3. Smoothing of, and parameter estimation from, noisy biophysical recordings.

    Directory of Open Access Journals (Sweden)

    Quentin J M Huys

    2009-05-01

    Full Text Available Biophysically detailed models of single cells are difficult to fit to real data. Recent advances in imaging techniques allow simultaneous access to various intracellular variables, and these data can be used to significantly facilitate the modelling task. These data, however, are noisy, and current approaches to building biophysically detailed models are not designed to deal with this. We extend previous techniques to take the noisy nature of the measurements into account. Sequential Monte Carlo ("particle filtering" methods, in combination with a detailed biophysical description of a cell, are used for principled, model-based smoothing of noisy recording data. We also provide an alternative formulation of smoothing where the neural nonlinearities are estimated in a non-parametric manner. Biophysically important parameters of detailed models (such as channel densities, intercompartmental conductances, input resistances, and observation noise are inferred automatically from noisy data via expectation-maximization. Overall, we find that model-based smoothing is a powerful, robust technique for smoothing of noisy biophysical data and for inference of biophysical parameters in the face of recording noise.

  4. Ballistic impact response of lipid membranes.

    Science.gov (United States)

    Zhang, Yao; Meng, Zhaoxu; Qin, Xin; Keten, Sinan

    2018-03-08

    Therapeutic agent loaded micro and nanoscale particles as high-velocity projectiles can penetrate cells and tissues, thereby serving as gene and drug delivery vehicles for direct and rapid internalization. Despite recent progress in developing micro/nanoscale ballistic tools, the underlying biophysics of how fast projectiles deform and penetrate cell membranes is still poorly understood. To understand the rate and size-dependent penetration processes, we present coarse-grained molecular dynamics simulations of the ballistic impact of spherical projectiles on lipid membranes. Our simulations reveal that upon impact, the projectile can pursue one of three distinct pathways. At low velocities below the critical penetration velocity, projectiles rebound off the surface. At intermediate velocities, penetration occurs after the projectile deforms the membrane into a tubular thread. At very high velocities, rapid penetration occurs through localized membrane deformation without tubulation. Membrane tension, projectile velocity and size govern which phenomenon occurs, owing to their positive correlation with the reaction force generated between the projectile and the membrane during impact. Two critical membrane tension values dictate the boundaries among the three pathways for a given system, due to the rate dependence of the stress generated in the membrane. Our findings provide broad physical insights into the ballistic impact response of soft viscous membranes and guide design strategies for drug delivery through lipid membranes using micro/nanoscale ballistic tools.

  5. Structure and biophysics

    CERN Document Server

    Puglisi, Joseph D

    2007-01-01

    This volume is a collection of articles from the proceedings of the ISSBMR 7th Course: Structure and Biophysics - New Technologies for Current Challenges in Biology and Beyond. This NATO Advanced Institute (ASI) was held in Erice at the Ettore Majorana Foundation and Centre for Scientific Culture on 22 June through 3 July 2005. The ASI brought together a diverse group of experts in the fields of Structural Biology, Biophysics and Physics. Prominent lecturers, from seven different countries, and students from around the world participated in the NATO ASI organized by Professors Joseph Puglisi (Stanford University, USA) and Alexander Arseniev (Moscow, RU). Advances in nuclear magnetic resonance spectroscopy (NMR) and x-ray crystallography have allowed the three-dimensional structures of many biological macromolecules and their complexes, including the ribosome and RNA polymerase to be solved. Fundamental principles of NMR spectroscopy and dynamics, x-ray crystallography, computation and experimental dynamics we...

  6. Role of the Transmembrane Potential in the Membrane Proton Leak

    Czech Academy of Sciences Publication Activity Database

    Ruprecht, A.; Sokolenko, E. A.; Beck, V.; Ninnemann, O.; Jabůrek, Martin; Trimbuch, T.; Klishin, S. S.; Ježek, Petr; Skulachev, V. P.; Pohl, E. E.

    2010-01-01

    Roč. 98, č. 8 (2010), s. 1503-1511 ISSN 0006-3495 R&D Projects: GA MŠk ME09018; GA ČR(CZ) GA303/07/0105 Institutional research plan: CEZ:AV0Z50110509 Keywords : proton leak * membrane potential * uncoupling proteins Subject RIV: BO - Biophysics Impact factor: 4.218, year: 2010

  7. Biophysics: for HTS hit validation, chemical lead optimization, and beyond.

    Science.gov (United States)

    Genick, Christine C; Wright, S Kirk

    2017-09-01

    There are many challenges to the drug discovery process, including the complexity of the target, its interactions, and how these factors play a role in causing the disease. Traditionally, biophysics has been used for hit validation and chemical lead optimization. With its increased throughput and sensitivity, biophysics is now being applied earlier in this process to empower target characterization and hit finding. Areas covered: In this article, the authors provide an overview of how biophysics can be utilized to assess the quality of the reagents used in screening assays, to validate potential tool compounds, to test the integrity of screening assays, and to create follow-up strategies for compound characterization. They also briefly discuss the utilization of different biophysical methods in hit validation to help avoid the resource consuming pitfalls caused by the lack of hit overlap between biophysical methods. Expert opinion: The use of biophysics early on in the drug discovery process has proven crucial to identifying and characterizing targets of complex nature. It also has enabled the identification and classification of small molecules which interact in an allosteric or covalent manner with the target. By applying biophysics in this manner and at the early stages of this process, the chances of finding chemical leads with novel mechanisms of action are increased. In the future, focused screens with biophysics as a primary readout will become increasingly common.

  8. Cell-geometry-dependent changes in plasma membrane order direct stem cell signalling and fate

    Science.gov (United States)

    von Erlach, Thomas C.; Bertazzo, Sergio; Wozniak, Michele A.; Horejs, Christine-Maria; Maynard, Stephanie A.; Attwood, Simon; Robinson, Benjamin K.; Autefage, Hélène; Kallepitis, Charalambos; del Río Hernández, Armando; Chen, Christopher S.; Goldoni, Silvia; Stevens, Molly M.

    2018-03-01

    Cell size and shape affect cellular processes such as cell survival, growth and differentiation1-4, thus establishing cell geometry as a fundamental regulator of cell physiology. The contributions of the cytoskeleton, specifically actomyosin tension, to these effects have been described, but the exact biophysical mechanisms that translate changes in cell geometry to changes in cell behaviour remain mostly unresolved. Using a variety of innovative materials techniques, we demonstrate that the nanostructure and lipid assembly within the cell plasma membrane are regulated by cell geometry in a ligand-independent manner. These biophysical changes trigger signalling events involving the serine/threonine kinase Akt/protein kinase B (PKB) that direct cell-geometry-dependent mesenchymal stem cell differentiation. Our study defines a central regulatory role by plasma membrane ordered lipid raft microdomains in modulating stem cell differentiation with potential translational applications.

  9. With or without rafts? Alternative views on cell membranes.

    Science.gov (United States)

    Sevcsik, Eva; Schütz, Gerhard J

    2016-02-01

    The fundamental mechanisms of protein and lipid organization at the plasma membrane have continued to engage researchers for decades. Among proposed models, one idea has been particularly successful which assumes that sterol-dependent nanoscopic phases of different lipid chain order compartmentalize proteins, thereby modulating protein functionality. This model of membrane rafts has sustainably sparked the fields of membrane biophysics and biology, and shifted membrane lipids into the spotlight of research; by now, rafts have become an integral part of our terminology to describe a variety of cell biological processes. But is the evidence clear enough to continue supporting a theoretical concept which has resisted direct proof by observation for nearly twenty years? In this essay, we revisit findings that gave rise to and substantiated the raft hypothesis, discuss its impact on recent studies, and present alternative mechanisms to account for plasma membrane heterogeneity. © 2015 WILEY Periodicals, Inc.

  10. Sphingolipid levels crucially modulate lateral microdomain organization of plasma membrane in living yeast

    Czech Academy of Sciences Publication Activity Database

    Večeř, J.; Veselá, Petra; Malínský, Jan; Herman, P.

    2014-01-01

    Roč. 588, č. 3 (2014), s. 443-449 ISSN 0014-5793 R&D Projects: GA ČR GAP205/12/0720 Institutional support: RVO:68378041 Keywords : membrane microdomain * lipid order * fluidity Subject RIV: BO - Biophysics Impact factor: 3.169, year: 2014

  11. Improvement of the accuracy by the measurement of the electrical cell membrane parameters

    Czech Academy of Sciences Publication Activity Database

    Rohlíček, Vojtěch; Rech, František

    2002-01-01

    Roč. 51, č. 2 (2002), s. 169-177 ISSN 0862-8408 Institutional research plan: CEZ:AV0Z5011922 Keywords : patch clamp technique * electrical parameters of the cell membrane * memebrane capacity Subject RIV: BO - Biophysics Impact factor: 0.984, year: 2002

  12. Radiation dosimetry and radiation biophysics

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    Radiation dosimetry and radiation biophysics are two closely integrated programs whose joint purpose is to explore the connections between the primary physical events produced by radiation and their biological consequences in cellular systems. The radiation dosimetry program includes the theoretical description of primary events and their connection with the observable biological effects. This program also is concerned with the design and measurement of physical parameters used in theory or to support biological experiments. The radiation biophysics program tests and uses the theoretical developments for experimental design, and provides information for further theoretical development through experiments on cellular systems

  13. Radiation dosimetry and radiation biophysics

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    Radiation dosimetry and radiation biophysics are two closely integrated programs whose joint purpose is to explore the connections between the primary physical events produced by radiation and their biological consequences in cellular systems. The radiation dosimetry program includes the theoretical description of primary events and their connection with the observable biological effects. This program also is concerned with design and measurement of those physical parameters used in the theory or to support biological experiments. The radiation biophysics program tests and makes use of the theoretical developments for experimental design. Also, this program provides information for further theoretical development through experiments on cellular systems

  14. Screening and large-scale expression of membrane proteins in mammalian cells for structural studies

    OpenAIRE

    Goehring, April; Lee, Chia-Hsueh; Wang, Kevin H.; Michel, Jennifer Carlisle; Claxton, Derek P.; Baconguis, Isabelle; Althoff, Thorsten; Fischer, Suzanne; Garcia, K. Christopher; Gouaux, Eric

    2014-01-01

    Structural, biochemical and biophysical studies of eukaryotic membrane proteins are often hampered by difficulties in over-expression of the candidate molecule. Baculovirus transduction of mammalian cells (BacMam), although a powerful method to heterologously express membrane proteins, can be cumbersome for screening and expression of multiple constructs. We therefore developed plasmid Eric Gouaux (pEG) BacMam, a vector optimized for use in screening assays, as well as for efficient productio...

  15. Membrane transport mechanism 3D structure and beyond

    CERN Document Server

    Ziegler, Christine

    2014-01-01

    This book provides a molecular view of membrane transport by means of numerous biochemical and biophysical techniques. The rapidly growing number of atomic structures of transporters in different conformations and the constant progress in bioinformatics have recently added deeper insights.   The unifying mechanism of energized solute transport across membranes is assumed to consist of the conformational cycling of a carrier protein to provide access to substrate binding sites from either side of a cellular membrane. Due to the central role of active membrane transport there is considerable interest in deciphering the principles of one of the most fundamental processes in nature: the alternating access mechanism.   This book brings together particularly significant structure-function studies on a variety of carrier systems from different transporter families: Glutamate symporters, LeuT-like fold transporters, MFS transporters and SMR (RND) exporters, as well as ABC-type importers.   The selected examples im...

  16. Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations.

    Science.gov (United States)

    Marcoline, Frank V; Bethel, Neville; Guerriero, Christopher J; Brodsky, Jeffrey L; Grabe, Michael

    2015-08-04

    The electrostatic properties of membrane proteins often reveal many of their key biophysical characteristics, such as ion channel selectivity and the stability of charged membrane-spanning segments. The Poisson-Boltzmann (PB) equation is the gold standard for calculating protein electrostatics, and the software APBSmem enables the solution of the PB equation in the presence of a membrane. Here, we describe significant advances to APBSmem, including full automation of system setup, per-residue energy decomposition, incorporation of PDB2PQR, calculation of membrane-induced pKa shifts, calculation of non-polar energies, and command-line scripting for large-scale calculations. We highlight these new features with calculations carried out on a number of membrane proteins, including the recently solved structure of the ion channel TRPV1 and a large survey of 1,614 membrane proteins of known structure. This survey provides a comprehensive list of residues with large electrostatic penalties for being embedded in the membrane, potentially revealing interesting functional information. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. How To Tackle the Issues in Free Energy Simulations of Long Amphiphiles Interacting with Lipid Membranes: Convergence and Local Membrane Deformations

    DEFF Research Database (Denmark)

    Filipe, H. A. L.; Moreno, M. J.; Rog, T.

    2014-01-01

    One of the great challenges in membrane biophysics is to find a means to foster the transport of drugs across complex membrane structures. In this spirit, we elucidate methodological challenges associated with free energy computations of complex chainlike molecules across lipid membranes....... As an appropriate standard molecule to this end, we consider 7-nitrobenz-2-oxa-1,3-diazol-4-yl-labeled fatty amine, NBD-C-n, which is here dealt with as a homologous series with varying chain lengths. We found the membrane-water interface region to be highly sensitive to details in free energy computations. Despite...... of radius 1.7 nm from the amphiphile. Importantly, the free energy results given by PGC were found to be qualitatively consistent with experimental data, while the PGD results were not. We conclude that with long amphiphiles there is reason for concern with regard to computations of their free energy...

  18. The biophysics of neuronal growth

    International Nuclear Information System (INIS)

    Franze, Kristian; Guck, Jochen

    2010-01-01

    For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.

  19. Biophysical regulation of stem cell differentiation.

    Science.gov (United States)

    Govey, Peter M; Loiselle, Alayna E; Donahue, Henry J

    2013-06-01

    Bone adaptation to its mechanical environment, from embryonic through adult life, is thought to be the product of increased osteoblastic differentiation from mesenchymal stem cells. In parallel with tissue-scale loading, these heterogeneous populations of multipotent stem cells are subject to a variety of biophysical cues within their native microenvironments. Bone marrow-derived mesenchymal stem cells-the most broadly studied source of osteoblastic progenitors-undergo osteoblastic differentiation in vitro in response to biophysical signals, including hydrostatic pressure, fluid flow and accompanying shear stress, substrate strain and stiffness, substrate topography, and electromagnetic fields. Furthermore, stem cells may be subject to indirect regulation by mechano-sensing osteocytes positioned to more readily detect these same loading-induced signals within the bone matrix. Such paracrine and juxtacrine regulation of differentiation by osteocytes occurs in vitro. Further studies are needed to confirm both direct and indirect mechanisms of biophysical regulation within the in vivo stem cell niche.

  20. A Novel Soluble Peptide with pH-Responsive Membrane Insertion.

    Science.gov (United States)

    Nguyen, Vanessa P; Alves, Daiane S; Scott, Haden L; Davis, Forrest L; Barrera, Francisco N

    2015-11-03

    Several diseases, such as cancer, are characterized by acidification of the extracellular environment. Acidosis can be employed as a target to specifically direct therapies to the diseased tissue. We have used first principles to design an acidity-triggered rational membrane (ATRAM) peptide with high solubility in solution that is able to interact with lipid membranes in a pH-dependent fashion. Biophysical studies show that the ATRAM peptide binds to the surface of lipid membranes at pH 8.0. However, acidification leads to the peptide inserting into the lipid bilayer as a transmembrane α-helix. The insertion of ATRAM into membranes occurs at a moderately acidic pH (with a pK of 6.5), similar to the extracellular pH found in solid tumors. Studies with human cell lines showed a highly efficient pH-dependent membrane targeting, without causing toxicity. Here we show that it is possible to rationally design a soluble peptide that selectively targets cell membranes in acidic environments.

  1. The relationship between fetal biophysical profile and cord blood PH

    Directory of Open Access Journals (Sweden)

    Valadan M

    2009-02-01

    Full Text Available "nBackground: The Biophysical Profile (BPP is a noninvasive test that predicts the presence or absence of fetal asphyxia and, ultimately, the risk of fetal death in the antenatal period. Intervention on the basis of an abnormal biophysical profile result has been reported to yield a significant reduction in prenatal mortality, and an association exists between biophysical profile scoring and a decreased cerebral palsy rate in a given population. The BPP evaluates five characteristics: fetal movement, tone, breathing, heart reactivity, and amniotic fluid (AF volume estimation. The purpose of study was to determine whether there are different degree of acidosis at which the biophysical activity (acute marker are affected. "nMethods: In a prospective study of 140 patients undergoing cesarean section before onset of labor, the fetal biophysical profile was performed 24h before the time of cesarean and was matched with cord arterial PH that was obtained from a cord segment (10-20cm that was double clamped after delivery of newborn. (using cord arterial PH less than 7.20 for the diagnosis of acidosis. "nResults: The fetal biophysical profile was found to have a significant relationship with umbilical blood PH. The sensitivity, specificity, positive predictive value, negative predictive value of fetal biophysical profile score were: 88.9%, 88.6%, 50%, 98.1%. "nConclusion: The first manifestations of fetal acidosis are nonreactive nonstress testing and fetal breathing loss; in advanced acidemia fetal movements and fetal tone are compromised. A protocol of antepartum fetal evaluation is suggested based upon the individual biophysical components rather than the score alone.

  2. Biophysical Evaluation of SonoSteam®:

    DEFF Research Database (Denmark)

    Andersen, Ann Zahle; Duelund, Lars; Brewer, Jonathan R.

    and safety evaluations. Our results show that there are no contradictions between data obtained by either approach. However, the biophysical methods draw a much more nuanced picture of the effects and efficiency of the investigated decontamination method, revealing e.g. an exponential dose/response...... relationship between SonoSteam treatment time and changes in collagen I, and a depth dependency in bacterial reduction, which points toward CFU counts overestimating total bacterial reduction. In conclusion the biophysical methods provide a less biased, reproducible and highly detailed system description...

  3. Cholesterol modulates CFTR confinement in the plasma membrane of primary epithelial cells.

    Science.gov (United States)

    Abu-Arish, Asmahan; Pandzic, Elvis; Goepp, Julie; Matthes, Elizabeth; Hanrahan, John W; Wiseman, Paul W

    2015-07-07

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma-membrane anion channel that, when mutated, causes the disease cystic fibrosis. Although CFTR has been detected in a detergent-resistant membrane fraction prepared from airway epithelial cells, suggesting that it may partition into cholesterol-rich membrane microdomains (lipid rafts), its compartmentalization has not been demonstrated in intact cells and the influence of microdomains on CFTR lateral mobility is unknown. We used live-cell imaging, spatial image correlation spectroscopy, and k-space image correlation spectroscopy to examine the aggregation state of CFTR and its dynamics both within and outside microdomains in the plasma membrane of primary human bronchial epithelial cells. These studies were also performed during treatments that augment or deplete membrane cholesterol. We found two populations of CFTR molecules that were distinguishable based on their dynamics at the cell surface. One population showed confinement and had slow dynamics that were highly cholesterol dependent. The other, more abundant population was less confined and diffused more rapidly. Treatments that deplete the membrane of cholesterol caused the confined fraction and average number of CFTR molecules per cluster to decrease. Elevating cholesterol had the opposite effect, increasing channel aggregation and the fraction of channels displaying confinement, consistent with CFTR recruitment into cholesterol-rich microdomains with dimensions below the optical resolution limit. Viral infection caused the nanoscale microdomains to fuse into large platforms and reduced CFTR mobility. To our knowledge, these results provide the first biophysical evidence for multiple CFTR populations and have implications for regulation of their surface expression and channel function. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. Biophysical Cancer Transformation Pathway

    Czech Academy of Sciences Publication Activity Database

    Pokorný, Jiří

    2009-01-01

    Roč. 28, č. 2 (2009), s. 105-123 ISSN 1536-8378 Institutional research plan: CEZ:AV0Z20670512 Keywords : Biophysics * Cancer * Electromagnetic fields Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 0.729, year: 2009

  5. Adaptive transition rates in excitable membranes

    Directory of Open Access Journals (Sweden)

    Shimon Marom

    2009-02-01

    Full Text Available Adaptation of activity in excitable membranes occurs over a wide range of timescales. Standard computational approaches handle this wide temporal range in terms of multiple states and related reaction rates emanating from the complexity of ionic channels. The study described here takes a different (perhaps complementary approach, by interpreting ion channel kinetics in terms of population dynamics. I show that adaptation in excitable membranes is reducible to a simple Logistic-like equation in which the essential non-linearity is replaced by a feedback loop between the history of activation and an adaptive transition rate that is sensitive to a single dimension of the space of inactive states. This physiologically measurable dimension contributes to the stability of the system and serves as a powerful modulator of input-output relations that depends on the patterns of prior activity; an intrinsic scale free mechanism for cellular adaptation that emerges from the microscopic biophysical properties of ion channels of excitable membranes.

  6. Molecular properties of steroids involved in their effects on the biophysical state of membranes.

    Science.gov (United States)

    Wenz, Jorge J

    2015-10-01

    The activity of steroids on membranes was studied in relation to their ordering, rigidifying, condensing and/or raft promoting ability. The structures of 82 steroids were modeled by a semi-empirical procedure (AM1) and 245 molecular descriptors were next computed on the optimized energy conformations. Principal component analysis, mean contrasting and logistic regression were used to correlate the molecular properties with 212 cases of documented activities. It was possible to group steroids based on their properties and activities, indicating that steroids having similar molecular properties have similar activities on membranes. Steroids having high values of area, partition coefficient, volume, number of rotatable bonds, molar refractivity, polarizability or mass displayed ordering, rigidifying, condensing and/or raft promoting activity on membranes higher than those steroids having low values in such molecular properties. After a variable selection procedure circumventing correlation problems among descriptors, area and log P were found as the most relevant properties in governing and predicting the activity of steroids on membranes. A logistic regression model as a function of the area and log P of the steroids is proposed, which is able to predict correctly 92.5% of the cases. A rationale of the findings is discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Characterising antimicrobial protein-membrane complexes

    International Nuclear Information System (INIS)

    Xun, Gloria; Dingley, Andrew; Tremouilhac, Pierre

    2009-01-01

    Full text: Antimicrobial proteins (AMPs) are host defence molecules that protect organisms from microbial infection. A number of hypotheses for AMP activity have been proposed which involve protein membrane interactions. However, there is a paucity of information describing AMP-membrane complexes in detail. The aim of this project is to characterise the interactions of amoebapore-A (APA-1) with membrane models using primarily solution-state NMR spectroscopy. APA-1 is an AMP which is regulated by a pH-dependent dimerisation event. Based on the atomic resolution solution structure of monomeric APA-1, it is proposed that this dimerisation is a prerequisite for ring-like hexameric pore formation. Due to the cytotoxicity of APA-1, we have developed a cell-free system to produce this protein. To facilitate our studies, we have adapted the cell-free system to isotope label APA-1. 13 C /15 N -enriched APA-1 sample was achieved and we have begun characterising APA-1 dimerisation and membrane interactions using NMR spectroscopy and other biochemical/biophysical methods. Neutron reflectometry is a surface-sensitive technique and therefore represents an ideal technique to probe how APA-1 interacts with membranes at the molecular level under different physiological conditions. Using Platypus, the pH-induced APA-1-membrane interactions should be detectable as an increase of the amount of protein adsorbed at the membrane surface and changes in the membrane properties. Specifically, detailed information of the structure and dimensions of the protein-membrane complex, the position and amount of the protein in the membrane, and the perturbation of the membrane phospholipids on protein incorporation can be extracted from the neutron reflectometry measurement. Such information will enable critical assessment of current proposed mechanisms of AMP activity in bacterial membranes and complement our NMR studies

  8. Overcoming bottlenecks in the membrane protein structural biology pipeline.

    Science.gov (United States)

    Hardy, David; Bill, Roslyn M; Jawhari, Anass; Rothnie, Alice J

    2016-06-15

    Membrane proteins account for a third of the eukaryotic proteome, but are greatly under-represented in the Protein Data Bank. Unfortunately, recent technological advances in X-ray crystallography and EM cannot account for the poor solubility and stability of membrane protein samples. A limitation of conventional detergent-based methods is that detergent molecules destabilize membrane proteins, leading to their aggregation. The use of orthologues, mutants and fusion tags has helped improve protein stability, but at the expense of not working with the sequence of interest. Novel detergents such as glucose neopentyl glycol (GNG), maltose neopentyl glycol (MNG) and calixarene-based detergents can improve protein stability without compromising their solubilizing properties. Styrene maleic acid lipid particles (SMALPs) focus on retaining the native lipid bilayer of a membrane protein during purification and biophysical analysis. Overcoming bottlenecks in the membrane protein structural biology pipeline, primarily by maintaining protein stability, will facilitate the elucidation of many more membrane protein structures in the near future. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  9. Effect of storage duration on the rheological properties of goose liquid egg products and eggshell membranes

    Czech Academy of Sciences Publication Activity Database

    Kumbár, V.; Nedomová, Š.; Trnka, Jan; Buchar, J.; Pytel, R.

    2016-01-01

    Roč. 95, č. 7 (2016), s. 1693-1701 ISSN 0032-5791 Institutional support: RVO:61388998 Keywords : egg yolk * albumen * liquid whole egg * rheology * eggshell membrane Subject RIV: BO - Biophysics Impact factor: 1.908, year: 2016 http://ps.oxfordjournals.org/

  10. Nanodisc-Tm: Rapid functional assessment of nanodisc reconstituted membrane proteins by CPM assay.

    Science.gov (United States)

    Ashok, Yashwanth; Jaakola, Veli-Pekka

    2016-01-01

    Membrane proteins are generally unstable in detergents. Therefore, biochemical and biophysical studies of membrane proteins in lipidic environments provides a near native-like environment suitable for membrane proteins. However, manipulation of proteins embedded in lipid bilayer has remained difficult. Methods such as nanodiscs and lipid cubic phase have been developed for easy manipulation of membrane proteins and have yielded significant insights into membrane proteins. Traditionally functional reconstitution of receptors in nanodiscs has been studied with radioligands. We present a simple and faster method for studying the functionality of reconstituted membrane proteins for routine characterization of protein batches after initial optimization of suitable conditions using radioligands. The benefits of the method are •Faster and generic method to assess functional reconstitution of membrane proteins.•Adaptable in high throughput format (≥96 well format).•Stability measurement in near-native lipid environment and lipid dependent melting temperatures.

  11. Biophysical study of resin acid effects on phospholipid membrane structure and properties

    DEFF Research Database (Denmark)

    Jagalski, Vivien; Barker, Robert; Topgaard, Daniel

    2016-01-01

    Hydrophobic resin acids (RAs) are synthesized by conifer trees as part of their defense mechanisms. One of the functions of RAs in plant defense is suggested to be the perturbation of the cellular membrane. However, there is a vast diversity of chemical structures within this class of molecules, ...

  12. Refractive-index-based screening of membrane-protein-mediated transfer across biological membranes.

    Science.gov (United States)

    Brändén, Magnus; Tabaei, Seyed R; Fischer, Gerhard; Neutze, Richard; Höök, Fredrik

    2010-07-07

    Numerous membrane-transport proteins are major drug targets, and therefore a key ingredient in pharmaceutical development is the availability of reliable, efficient tools for membrane transport characterization and inhibition. Here, we present the use of evanescent-wave sensing for screening of membrane-protein-mediated transport across lipid bilayer membranes. This method is based on a direct recording of the temporal variations in the refractive index that occur upon a transfer-dependent change in the solute concentration inside liposomes associated to a surface plasmon resonance (SPR) active sensor surface. The applicability of the method is demonstrated by a functional study of the aquaglyceroporin PfAQP from the malaria parasite Plasmodium falciparum. Assays of the temperature dependence of facilitated diffusion of sugar alcohols on a single set of PfAQP-reconstituted liposomes reveal that the activation energies for facilitated diffusion of xylitol and sorbitol are the same as that previously measured for glycerol transport in the aquaglyceroporin of Escherichia coli (5 kcal/mole). These findings indicate that the aquaglyceroporin selectivity filter does not discriminate sugar alcohols based on their length, and that the extra energy cost of dehydration of larger sugar alcohols, upon entering the pore, is compensated for by additional hydrogen-bond interactions within the aquaglyceroporin pore. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  13. Neutrons and model membranes

    Science.gov (United States)

    Fragneto, G.

    2012-11-01

    Current research in membrane protein biophysics highlights the emerging role of lipids in shaping membrane protein function. Cells and organisms have developed sophisticated mechanisms for controlling the lipid composition and many diseases are related to the failure of these mechanisms. One of the recent advances in the field is the discovery of the existence of coexisting micro-domains within a single membrane, important for regulating some signaling pathways. Many important properties of these domains remain poorly characterized. The characterization and analysis of bio-interfaces represent a challenge. Performing measurements on these few nanometer thick, soft, visco-elastic and dynamic systems is close to the limits of the available tools and methods. Neutron scattering techniques including small angle scattering, diffraction, reflectometry as well as inelastic methods are rapidly developing for these studies and are attracting an increasing number of biologists and biophysicists at large facilities. This manuscript will review some recent progress in the field and provide perspectives for future developments. It aims at highlighting neutron reflectometry as a versatile method to tackle questions dealing with the understanding and function of biomembranes and their components. The other important scattering methods are only briefly introduced.

  14. Evaluation of biophysical skin parameters and assessment of hair growth in patients with acne treated with isotretinoin.

    Science.gov (United States)

    Kmieć, Małgorzata L; Pajor, Anna; Broniarczyk-Dyła, Grażyna

    2013-12-01

    Treatment of the severe forms of acne vulgaris remains a challenge. Isotretinoin is a drug often used in these cases. Retinoids affect the mechanisms that play a role in the pathogenesis of acne, reduce the production of sebum and sizes of the sebaceous glands. However, isotretinoin appears to have undesirable side effects in the skin, mucous membranes and hair. THE AIM OF THIS STUDY WAS TO ASSESS THE EFFECT OF ACNE VULGARIS TREATMENT WITH ISOTRETINOIN ON BIOPHYSICAL SKIN PARAMETERS: skin sebum and stratum corneum hydration levels, transepidermal water loss values, pH, erythema and hair growth parameters: total number, density and proportion of anagen hair. THE STUDY INCLUDED THIRTY PATIENTS WITH ACNE TYPES: papulopustular, conglobata and phlegmonosa. Patients were treated with isotretinoin at a dose of 0.5-1.0 mg/kg/day for a period of 4-7 months. The measurements of skin biophysical parameters were performed before and after the treatment using Sebumeter SM815, Corneometer CM825, Tewameter TM300, MX Mexameter MX18 and Skin-pH-Meter PH908. Hair growth parameters were evaluated with FotoFinder Dermoscope using the TrichoScan Professional V3.0.8.76 software. The results of biophysical skin parameter measurements after the treatment showed a reduction in the severity of seborrhea. However, the skin was dry, which confirmed a lowered degree of stratum corneum hydration and an increase in transepidermal water loss values. Moreover, severity of erythema, an increase in pH value, and variations in selected hair growth parameters: decrease in total count, density and proportion of anagen hair were demonstrated. The reduction in the skin sebum levels was observed after the treatment. There was dryness of the skin, which was confirmed by biophysical skin parameter measurements. Changes in the hair growth parameters showed telogen effluvium hair loss.

  15. Biophysically realistic minimal model of dopamine neuron

    Science.gov (United States)

    Oprisan, Sorinel

    2008-03-01

    We proposed and studied a new biophysically relevant computational model of dopaminergic neurons. Midbrain dopamine neurons are involved in motivation and the control of movement, and have been implicated in various pathologies such as Parkinson's disease, schizophrenia, and drug abuse. The model we developed is a single-compartment Hodgkin-Huxley (HH)-type parallel conductance membrane model. The model captures the essential mechanisms underlying the slow oscillatory potentials and plateau potential oscillations. The main currents involved are: 1) a voltage-dependent fast calcium current, 2) a small conductance potassium current that is modulated by the cytosolic concentration of calcium, and 3) a slow voltage-activated potassium current. We developed multidimensional bifurcation diagrams and extracted the effective domains of sustained oscillations. The model includes a calcium balance due to the fundamental importance of calcium influx as proved by simultaneous electrophysiological and calcium imaging procedure. Although there are significant evidences to suggest a partially electrogenic calcium pump, all previous models considered only elecrtogenic pumps. We investigated the effect of the electrogenic calcium pump on the bifurcation diagram of the model and compared our findings against the experimental results.

  16. Global energy modeling - A biophysical approach

    Energy Technology Data Exchange (ETDEWEB)

    Dale, Michael

    2010-09-15

    This paper contrasts the standard economic approach to energy modelling with energy models using a biophysical approach. Neither of these approaches includes changing energy-returns-on-investment (EROI) due to declining resource quality or the capital intensive nature of renewable energy sources. Both of these factors will become increasingly important in the future. An extension to the biophysical approach is outlined which encompasses a dynamic EROI function that explicitly incorporates technological learning. The model is used to explore several scenarios of long-term future energy supply especially concerning the global transition to renewable energy sources in the quest for a sustainable energy system.

  17. Molecular Transport Studies Through Unsupported Lipid Membranes

    Science.gov (United States)

    Rock, William; Parekh, Sapun; Bonn, Mischa

    2014-03-01

    Dendrimers, spherical polymeric nanoparticles made from branched monomers around a central core, show great promise as drug delivery vehicles. Dendrimer size, core contents, and surface functionality can be synthetically tuned, providing unprecedented versatility. Polyamidoamine (PAMAM) dendrimers have been shown to enter cells; however, questions remain about their biophysical interactions with the cell membrane, specifically about the presence and size of transient pores. We monitor dendrimer-lipid bilayer interactions using unsupported black lipid membranes (BLMs) as model cell membranes. Custom bilayer slides contain two vertically stacked aqueous chambers separated by a 25 μm Teflon sheet with a 120 μm aperture where the bilayer is formed. We vary the composition of model membranes (cholesterol content and lipid phase) to create biomimetic systems and study the interaction of PAMAM G6 and G3 dendrimers with these bilayers. Dendrimers, dextran cargo, and bilayers are monitored and quantified using time-lapse fluorescence imaging. Electrical capacitance measurements are simultaneously recorded to determine if the membrane is porous, and the pore size is deduced by monitoring transport of fluorescent dextrans of increasing molecular weight. These experiments shed light on the importance of cholesterol content and lipid phase on the interaction of dendrimer nanoparticles with membranes.

  18. Biophysical Regulation of Vascular Differentiation and Assembly

    CERN Document Server

    Gerecht, Sharon

    2011-01-01

    The ability to grow stem cells in the laboratory and to guide their maturation to functional cells allows us to study the underlying mechanisms that govern vasculature differentiation and assembly in health and disease. Accumulating evidence suggests that early stages of vascular growth are exquisitely tuned by biophysical cues from the microenvironment, yet the scientific understanding of such cellular environments is still in its infancy. Comprehending these processes sufficiently to manipulate them would pave the way to controlling blood vessel growth in therapeutic applications. This book assembles the works and views of experts from various disciplines to provide a unique perspective on how different aspects of its microenvironment regulate the differentiation and assembly of the vasculature. In particular, it describes recent efforts to exploit modern engineering techniques to study and manipulate various biophysical cues. Biophysical Regulation of Vascular Differentiation and Assembly provides an inter...

  19. Biophysics and systems biology.

    Science.gov (United States)

    Noble, Denis

    2010-03-13

    Biophysics at the systems level, as distinct from molecular biophysics, acquired its most famous paradigm in the work of Hodgkin and Huxley, who integrated their equations for the nerve impulse in 1952. Their approach has since been extended to other organs of the body, notably including the heart. The modern field of computational biology has expanded rapidly during the first decade of the twenty-first century and, through its contribution to what is now called systems biology, it is set to revise many of the fundamental principles of biology, including the relations between genotypes and phenotypes. Evolutionary theory, in particular, will require re-assessment. To succeed in this, computational and systems biology will need to develop the theoretical framework required to deal with multilevel interactions. While computational power is necessary, and is forthcoming, it is not sufficient. We will also require mathematical insight, perhaps of a nature we have not yet identified. This article is therefore also a challenge to mathematicians to develop such insights.

  20. Large-scale biophysical evaluation of protein PEGylation effects

    DEFF Research Database (Denmark)

    Vernet, Erik; Popa, Gina; Pozdnyakova, Irina

    2016-01-01

    PEGylation is the most widely used method to chemically modify protein biopharmaceuticals, but surprisingly limited public data is available on the biophysical effects of protein PEGylation. Here we report the first large-scale study, with site-specific mono-PEGylation of 15 different proteins...... of PEGylation on the thermal stability of a protein based on data generated by circular dichroism (CD), differential scanning calorimetry (DSC), or differential scanning fluorimetry (DSF). In addition, DSF was validated as a fast and inexpensive screening method for thermal unfolding studies of PEGylated...... proteins. Multivariate data analysis revealed clear trends in biophysical properties upon PEGylation for a subset of proteins, although no universal trends were found. Taken together, these findings are important in the consideration of biophysical methods and evaluation of second...

  1. Effect of heavy water on phospholipid membranes: experimental confirmation of molecular dynamics simulations

    Czech Academy of Sciences Publication Activity Database

    Beranová, Lenka; Humpolíčková, Jana; Sýkora, Jan; Benda, Aleš; Cwiklik, Lukasz; Jurkiewicz, Piotr; Gröbner, G.; Hof, Martin

    Roč. 14, č. 42 ( 2012 ), s. 14516-14522 ISSN 1463-9076 R&D Projects: GA AV ČR GEMEM/09/E006; GA ČR GBP208/12/G016 Institutional support: RVO:61388955 Keywords : phospholipid membranes * biophysics * physical chemistry Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.829, year: 2012

  2. Biophysical models of larval dispersal in the Benguela Current ...

    African Journals Online (AJOL)

    We synthesise and update results from the suite of biophysical, larval-dispersal models developed in the Benguela Current ecosystem. Biophysical models of larval dispersal use outputs of physical hydrodynamic models as inputs to individual-based models in which biological processes acting during the larval life are ...

  3. Delineating Biophysical Environments of the Sunda Banda Seascape, Indonesia

    Directory of Open Access Journals (Sweden)

    Mingshu Wang

    2015-01-01

    Full Text Available The Sunda Banda Seascape (SBS, located in the center of the Coral Triangle, is a global center of marine biodiversity and a conservation priority. We proposed the first biophysical environmental delineation of the SBS using globally available satellite remote sensing and model-assimilated data to categorize this area into unique and meaningful biophysical classes. Specifically, the SBS was partitioned into eight biophysical classes characterized by similar sea surface temperature, chlorophyll a concentration, currents, and salinity patterns. Areas within each class were expected to have similar habitat types and ecosystem functions. Our work supplemented prevailing global marine management schemes by focusing in on a regional scale with finer spatial resolution. It also provided a baseline for academic research, ecological assessments and will facilitate marine spatial planning and conservation activities in the area. In addition, the framework and methods of delineating biophysical environments we presented can be expanded throughout the whole Coral Triangle to support research and conservation activities in this important region.

  4. Periplasmic quality control in biogenesis of outer membrane proteins.

    Science.gov (United States)

    Lyu, Zhi Xin; Zhao, Xin Sheng

    2015-04-01

    The β-barrel outer membrane proteins (OMPs) are integral membrane proteins that reside in the outer membrane of Gram-negative bacteria and perform a diverse range of biological functions. Synthesized in the cytoplasm, OMPs must be transported across the inner membrane and through the periplasmic space before they are assembled in the outer membrane. In Escherichia coli, Skp, SurA and DegP are the most prominent factors identified to guide OMPs across the periplasm and to play the role of quality control. Although extensive genetic and biochemical analyses have revealed many basic functions of these periplasmic proteins, the mechanism of their collaboration in assisting the folding and insertion of OMPs is much less understood. Recently, biophysical approaches have shed light on the identification of the intricate network. In the present review, we summarize recent advances in the characterization of these key factors, with a special emphasis on the multifunctional protein DegP. In addition, we present our proposed model on the periplasmic quality control in biogenesis of OMPs.

  5. Structural biophysics

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    Summaries of research projects conducted during 1978 and 1979 are presented. The structural biophysics group explores the high-resolution structure of biological macromolecules and cell organelles. Specific subject areas include: the basic characteristics of photosynthesis in plants; the chemical composition of individual fly ash particles at the site of their damaging action in tissues; direct analysis of frozen-hydrated biological samples by scanning electron microscopy; yeast genetics; the optical activity of DNA aggregates; measurement and characterization of lipoproteins; function of lipoproteins; and the effect of radiation and pollutants on mammalian cells

  6. How membrane lipids control the 3D structure and function of receptors

    Directory of Open Access Journals (Sweden)

    Jacques Fantini

    2018-02-01

    Full Text Available The cohabitation of lipids and proteins in the plasma membrane of mammalian cells is controlled by specific biochemical and biophysical rules. Lipids may be either constitutively tightly bound to cell-surface receptors (non-annular lipids or less tightly attached to the external surface of the protein (annular lipids. The latter are exchangeable with surrounding bulk membrane lipids on a faster time scale than that of non-annular lipids. Not only do non-annular lipids bind to membrane proteins through stereoselective mechanisms, they can also help membrane receptors acquire (or maintain a functional 3D structure. Cholesterol is the prototype of membrane lipids that finely controls the 3D structure and function of receptors. However, several other lipids such as sphingolipids may also modulate the function of membrane proteins though conformational adjustments. All these concepts are discussed in this review in the light of representative examples taken from the literature.

  7. Application of virus-like particles (VLP) to NMR characterization of viral membrane protein interactions

    Energy Technology Data Exchange (ETDEWEB)

    Antanasijevic, Aleksandar; Kingsley, Carolyn [University of Illinois at Chicago, Department of Biochemistry and Molecular Genetics (United States); Basu, Arnab; Bowlin, Terry L. [Microbiotix Inc. (United States); Rong, Lijun [University of Illinois at Chicago, Department of Microbiology and Immunology (United States); Caffrey, Michael, E-mail: caffrey@uic.edu [University of Illinois at Chicago, Department of Biochemistry and Molecular Genetics (United States)

    2016-03-15

    The membrane proteins of viruses play critical roles in the virus life cycle and are attractive targets for therapeutic intervention. Virus-like particles (VLP) present the possibility to study the biochemical and biophysical properties of viral membrane proteins in their native environment. Specifically, the VLP constructs contain the entire protein sequence and are comprised of native membrane components including lipids, cholesterol, carbohydrates and cellular proteins. In this study we prepare VLP containing full-length hemagglutinin (HA) or neuraminidase (NA) from influenza and characterize their interactions with small molecule inhibitors. Using HA-VLP, we first show that VLP samples prepared using the standard sucrose gradient purification scheme contain significant amounts of serum proteins, which exhibit high potential for non-specific interactions, thereby complicating NMR studies of ligand-target interactions. We then show that the serum contaminants may be largely removed with the addition of a gel filtration chromatography step. Next, using HA-VLP we demonstrate that WaterLOGSY NMR is significantly more sensitive than Saturation Transfer Difference (STD) NMR for the study of ligand interactions with membrane bound targets. In addition, we compare the ligand orientation to HA embedded in VLP with that of recombinant HA by STD NMR. In a subsequent step, using NA-VLP we characterize the kinetic and binding properties of substrate analogs and inhibitors of NA, including study of the H274Y-NA mutant, which leads to wide spread resistance to current influenza antivirals. In summary, our work suggests that VLP have high potential to become standard tools in biochemical and biophysical studies of viral membrane proteins, particularly when VLP are highly purified and combined with control VLP containing native membrane proteins.

  8. Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes.

    Science.gov (United States)

    Yáñez-Mó, María; Barreiro, Olga; Gordon-Alonso, Mónica; Sala-Valdés, Mónica; Sánchez-Madrid, Francisco

    2009-09-01

    Membrane lipids and proteins are non-randomly distributed and are unable to diffuse freely in the plane of the membrane. This is because of multiple constraints imposed both by the cortical cytoskeleton and by the preference of lipids and proteins to cluster into diverse and specialized membrane domains, including tetraspanin-enriched microdomains, glycosylphosphatidyl inositol-linked proteins nanodomains and caveolae, among others. Recent biophysical characterization of tetraspanin-enriched microdomains suggests that they might be specially suited for the regulation of avidity of adhesion receptors and the compartmentalization of enzymatic activities. Moreover, modulation by tetraspanins of the function of adhesion receptors involved in inflammation, lymphocyte activation, cancer and pathogen infection suggests potential as therapeutic targets. This review explores this emerging picture of tetraspanin microdomains and discusses the implications for cell adhesion, proteolysis and pathogenesis.

  9. Recent progress in Biophysics

    International Nuclear Information System (INIS)

    Bemski, G.

    1980-03-01

    Recent progress in biophysics is reviewed, and three examples of the use of physical techniques and ideas in biological research are given. The first one deals with the oxygen transporting protein-hemoglobin, the second one with photosynthesis, and the third one with image formation, using nuclear magnetic resonance. (Author) [pt

  10. Self-assembly of nanoscale particles with biosurfactants and membrane scaffold proteins.

    Science.gov (United States)

    Faas, Ramona; Pohle, Annelie; Moß, Karin; Henkel, Marius; Hausmann, Rudolf

    2017-12-01

    Nanodiscs are membrane mimetics which may be used as tools for biochemical and biophysical studies of a variety of membrane proteins. These nanoscale structures are composed of a phospholipid bilayer held together by an amphipathic membrane scaffold protein (MSP). In the past, nanodiscs were successfully assembled with membrane scaffold protein 1D1 and 1,2-dipalmitoyl- sn -glycero-3-phosphorylcholine with a homogeneous diameter of ∼10 nm. In this study, the formation of nanoscale particles from MSP1D1 and rhamnolipid biosurfactants is investigated. Different protein to lipid ratios of 1:80, 1:90 and 1:100 were used for the assembly reaction, which were consecutively separated, purified and analyzed by size-exclusion chromatography (SEC) and dynamic light scattering (DLS). Size distributions were measured to determine homogeneity and confirm size dimensions. In this study, first evidence is presented on the formation of nanoscale particles with rhamnolipid biosurfactants and membrane scaffold proteins.

  11. Characterization of a new series of fluorescent probes for imaging membrane order.

    Directory of Open Access Journals (Sweden)

    Joanna M Kwiatek

    Full Text Available Visualization and quantification of lipid order is an important tool in membrane biophysics and cell biology, but the availability of environmentally sensitive fluorescent membrane probes is limited. Here, we present the characterization of the novel fluorescent dyes PY3304, PY3174 and PY3184, whose fluorescence properties are sensitive to membrane lipid order. In artificial bilayers, the fluorescence emission spectra are red-shifted between the liquid-ordered and liquid-disordered phases. Using ratiometric imaging we demonstrate that the degree of membrane order can be quantitatively determined in artificial liposomes as well as live cells and intact, live zebrafish embryos. Finally, we show that the fluorescence lifetime of the dyes is also dependent on bilayer order. These probes expand the current palate of lipid order-sensing fluorophores affording greater flexibility in the excitation/emission wavelengths and possibly new opportunities in membrane biology.

  12. Molecular, biophysical, and pharmacological properties of calcium-activated chloride channels.

    Science.gov (United States)

    Kamaleddin, Mohammad Amin

    2018-02-01

    Calcium-activated chloride channels (CaCCs) are a family of anionic transmembrane ion channels. They are mainly responsible for the movement of Cl - and other anions across the biological membranes, and they are widely expressed in different tissues. Since the Cl - flow into or out of the cell plays a crucial role in hyperpolarizing or depolarizing the cells, respectively, the impact of intracellular Ca 2+ concentration on these channels is attracting a lot of attentions. After summarizing the molecular, biophysical, and pharmacological properties of CaCCs, the role of CaCCs in normal cellular functions will be discussed, and I will emphasize how dysregulation of CaCCs in pathological conditions can account for different diseases. A better understanding of CaCCs and a pivotal regulatory role of Ca 2+ can shed more light on the therapeutic strategies for different neurological disorders that arise from chloride dysregulation, such as asthma, cystic fibrosis, and neuropathic pain. © 2017 Wiley Periodicals, Inc.

  13. Interactions of Ras proteins with the plasma membrane and their roles in signaling.

    Science.gov (United States)

    Eisenberg, Sharon; Henis, Yoav I

    2008-01-01

    The complex dynamic structure of the plasma membrane plays critical roles in cellular signaling; interactions with the membrane lipid milieu, spatial segregation within and between cellular membranes and/or targeting to specific membrane-associated scaffolds are intimately involved in many signal transduction pathways. In this review, we focus on the membrane interactions of Ras proteins. These small GTPases play central roles in the regulation of cell growth and proliferation, and their excessive activation is commonly encountered in human tumors. Ras proteins associate with the membrane continuously via C-terminal lipidation and additional interactions in both their inactive and active forms; this association, as well as the targeting of specific Ras isoforms to plasma membrane microdomains and to intracellular organelles, have recently been implicated in Ras signaling and oncogenic potential. We discuss biochemical and biophysical evidence for the roles of specific domains of Ras proteins in mediating their association with the plasma membrane, and consider the potential effects of lateral segregation and interactions with membrane-associated protein assemblies on the signaling outcomes.

  14. MODELLING BIOPHYSICAL PARAMETERS OF MAIZE USING LANDSAT 8 TIME SERIES

    Directory of Open Access Journals (Sweden)

    T. Dahms

    2016-06-01

    Full Text Available Open and free access to multi-frequent high-resolution data (e.g. Sentinel – 2 will fortify agricultural applications based on satellite data. The temporal and spatial resolution of these remote sensing datasets directly affects the applicability of remote sensing methods, for instance a robust retrieving of biophysical parameters over the entire growing season with very high geometric resolution. In this study we use machine learning methods to predict biophysical parameters, namely the fraction of absorbed photosynthetic radiation (FPAR, the leaf area index (LAI and the chlorophyll content, from high resolution remote sensing. 30 Landsat 8 OLI scenes were available in our study region in Mecklenburg-Western Pomerania, Germany. In-situ data were weekly to bi-weekly collected on 18 maize plots throughout the summer season 2015. The study aims at an optimized prediction of biophysical parameters and the identification of the best explaining spectral bands and vegetation indices. For this purpose, we used the entire in-situ dataset from 24.03.2015 to 15.10.2015. Random forest and conditional inference forests were used because of their explicit strong exploratory and predictive character. Variable importance measures allowed for analysing the relation between the biophysical parameters with respect to the spectral response, and the performance of the two approaches over the plant stock evolvement. Classical random forest regression outreached the performance of conditional inference forests, in particular when modelling the biophysical parameters over the entire growing period. For example, modelling biophysical parameters of maize for the entire vegetation period using random forests yielded: FPAR: R² = 0.85; RMSE = 0.11; LAI: R² = 0.64; RMSE = 0.9 and chlorophyll content (SPAD: R² = 0.80; RMSE=4.9. Our results demonstrate the great potential in using machine-learning methods for the interpretation of long-term multi-frequent remote sensing

  15. Modelling Biophysical Parameters of Maize Using Landsat 8 Time Series

    Science.gov (United States)

    Dahms, Thorsten; Seissiger, Sylvia; Conrad, Christopher; Borg, Erik

    2016-06-01

    Open and free access to multi-frequent high-resolution data (e.g. Sentinel - 2) will fortify agricultural applications based on satellite data. The temporal and spatial resolution of these remote sensing datasets directly affects the applicability of remote sensing methods, for instance a robust retrieving of biophysical parameters over the entire growing season with very high geometric resolution. In this study we use machine learning methods to predict biophysical parameters, namely the fraction of absorbed photosynthetic radiation (FPAR), the leaf area index (LAI) and the chlorophyll content, from high resolution remote sensing. 30 Landsat 8 OLI scenes were available in our study region in Mecklenburg-Western Pomerania, Germany. In-situ data were weekly to bi-weekly collected on 18 maize plots throughout the summer season 2015. The study aims at an optimized prediction of biophysical parameters and the identification of the best explaining spectral bands and vegetation indices. For this purpose, we used the entire in-situ dataset from 24.03.2015 to 15.10.2015. Random forest and conditional inference forests were used because of their explicit strong exploratory and predictive character. Variable importance measures allowed for analysing the relation between the biophysical parameters with respect to the spectral response, and the performance of the two approaches over the plant stock evolvement. Classical random forest regression outreached the performance of conditional inference forests, in particular when modelling the biophysical parameters over the entire growing period. For example, modelling biophysical parameters of maize for the entire vegetation period using random forests yielded: FPAR: R² = 0.85; RMSE = 0.11; LAI: R² = 0.64; RMSE = 0.9 and chlorophyll content (SPAD): R² = 0.80; RMSE=4.9. Our results demonstrate the great potential in using machine-learning methods for the interpretation of long-term multi-frequent remote sensing datasets to model

  16. Novel physical chemistry approaches in biophysical researches with advanced application of lasers: Detection and manipulation.

    Science.gov (United States)

    Iwata, Koichi; Terazima, Masahide; Masuhara, Hiroshi

    2018-02-01

    Novel methodologies utilizing pulsed or intense CW irradiation obtained from lasers have a major impact on biological sciences. In this article, recent development in biophysical researches fully utilizing the laser irradiation is described for three topics, time-resolved fluorescence spectroscopy, time-resolved thermodynamics, and manipulation of the biological assemblies by intense laser irradiation. First, experimental techniques for time-resolved fluorescence spectroscopy are concisely explained in Section 2. As an example of the recent application of time-resolved fluorescence spectroscopy to biological systems, evaluation of the viscosity of lipid bilayer membranes is described. The results of the spectroscopic experiments strongly suggest the presence of heterogeneous membrane structure with two different viscosity values in liposomes formed by a single phospholipid. Section 3 covers the time-resolved thermodynamics. Thermodynamical properties are important to characterize biomolecules. However, measurement of these quantities for short-lived intermediate species has been impossible by traditional thermodynamical techniques. Recently, development of a spectroscopic method based on the transient grating method enables us to measure these quantities and also to elucidate reaction kinetics which cannot be detected by other spectroscopic methods. The principle of the measurements and applications to some protein reactions are reviewed. Manipulation and fabrication of supramolecues, amino acids, proteins, and living cells by intense laser irradiation are described in Section 4. Unconventional assembly, crystallization and growth, amyloid fibril formation, and living cell manipulation are achieved by CW laser trapping and femtosecond laser-induced cavitation bubbling. Their spatio-temporal controllability is opening a new avenue in the relevant molecular and bioscience research fields. This article is part of a Special Issue entitled "Biophysical Exploration of

  17. The catalytic function of cytochrome P450 is entwined with its membrane-bound nature [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Carlo Barnaba

    2017-05-01

    Full Text Available Cytochrome P450, a family of monooxygenase enzymes, is organized as a catalytic metabolon, which requires enzymatic partners as well as environmental factors that tune its complex dynamic. P450 and its reducing counterparts—cytochrome P450-reductase and cytochrome b5—are membrane-bound proteins located in the cytosolic side of the endoplasmic reticulum. They are believed to dynamically associate to form functional complexes. Increasing experimental evidence signifies the role(s played by both protein-protein and protein-lipid interactions in P450 catalytic function and efficiency. However, the biophysical challenges posed by their membrane-bound nature have severely limited high-resolution understanding of the molecular interfaces of these interactions. In this article, we provide an overview of the current knowledge on cytochrome P450, highlighting the environmental factors that are entwined with its metabolic function. Recent advances in structural biophysics are also discussed, setting up the bases for a new paradigm in the study of this important class of membrane-bound enzymes.

  18. Handbook of Single-Molecule Biophysics

    CERN Document Server

    Hinterdorfer, Peter

    2009-01-01

    The last decade has seen the development of a number of novel biophysical methods that allow the manipulation and study of individual biomolecules. The ability to monitor biological processes at this fundamental level of sensitivity has given rise to an improved understanding of the underlying molecular mechanisms. Through the removal of ensemble averaging, distributions and fluctuations of molecular properties can be characterized, transient intermediates identified, and catalytic mechanisms elucidated. By applying forces on biomolecules while monitoring their activity, important information can be obtained on how proteins couple function to structure. The Handbook of Single-Molecule Biophysics provides an introduction to these techniques and presents an extensive discussion of the new biological insights obtained from them. Coverage includes: Experimental techniques to monitor and manipulate individual biomolecules The use of single-molecule techniques in super-resolution and functional imaging Single-molec...

  19. Biophysical impacts of climate-smart agriculture in the Midwest United States.

    Science.gov (United States)

    Bagley, Justin E; Miller, Jesse; Bernacchi, Carl J

    2015-09-01

    The potential impacts of climate change in the Midwest United States present unprecedented challenges to regional agriculture. In response to these challenges, a variety of climate-smart agricultural methodologies have been proposed to retain or improve crop yields, reduce agricultural greenhouse gas emissions, retain soil quality and increase climate resilience of agricultural systems. One component that is commonly neglected when assessing the environmental impacts of climate-smart agriculture is the biophysical impacts, where changes in ecosystem fluxes and storage of moisture and energy lead to perturbations in local climate and water availability. Using a combination of observational data and an agroecosystem model, a series of climate-smart agricultural scenarios were assessed to determine the biophysical impacts these techniques have in the Midwest United States. The first scenario extended the growing season for existing crops using future temperature and CO2 concentrations. The second scenario examined the biophysical impacts of no-till agriculture and the impacts of annually retaining crop debris. Finally, the third scenario evaluated the potential impacts that the adoption of perennial cultivars had on biophysical quantities. Each of these scenarios was found to have significant biophysical impacts. However, the timing and magnitude of the biophysical impacts differed between scenarios. © 2014 John Wiley & Sons Ltd.

  20. Biophysics of molecular gastronomy.

    Science.gov (United States)

    Brenner, Michael P; Sörensen, Pia M

    2015-03-26

    Chefs and scientists exploring biophysical processes have given rise to molecular gastronomy. In this Commentary, we describe how a scientific understanding of recipes and techniques facilitates the development of new textures and expands the flavor palette. The new dishes that result engage our senses in unexpected ways. PAPERCLIP. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Biophysical analysis of the interaction of granulysin-derived peptides with enterobacterial endotoxins.

    Science.gov (United States)

    Chen, Xi; Howe, Jörg; Andrä, Jörg; Rössle, Manfred; Richter, Walter; da Silva, Ana Paula Galvão; Krensky, Alan M; Clayberger, Carol; Brandenburg, Klaus

    2007-10-01

    To combat infections by Gram-negative bacteria, it is not only necessary to kill the bacteria but also to neutralize pathogenicity factors such as endotoxin (lipopolysaccharide, LPS). The development of antimicrobial peptides based on mammalian endotoxin-binding proteins is a promising tool in the fight against bacterial infections, and septic shock syndrome. Here, synthetic peptides derived from granulysin (Gra-pep) were investigated in microbiological and biophysical assays to understand their interaction with LPS. We analyzed the influence of the binding of Gra-pep on (1) the acyl chain melting of the hydrophobic moiety of LPS, lipid A, by Fourier-transform spectroscopy, (2) the aggregate structure of LPS by small-angle X-ray scattering and cryo-transmission electron microscopy, and 3) the enthalpy change by isothermal titration calorimetry. In addition, the influence of Gra-pep on the incorporation of LPS and LPS-LBP (lipopolysaccharide-binding protein) complexes into negatively charged liposomes was monitored. Our findings demonstrate a characteristic change in the aggregate structure of LPS into multilamellar stacks in the presence of Gra-pep, but little or no change of acyl chain fluidity. Neutralization of LPS by Gra-pep is not due to a scavenging effect in solution, but rather proceeds after incorporation into target membranes, suggesting a requisite membrane-bound step.

  2. Dynamic membrane interactions of antibacterial and antifungal biomolecules, and amyloid peptides, revealed by solid-state NMR spectroscopy.

    Science.gov (United States)

    Naito, Akira; Matsumori, Nobuaki; Ramamoorthy, Ayyalusamy

    2018-02-01

    A variety of biomolecules acting on the cell membrane folds into a biologically active structure in the membrane environment. It is, therefore, important to determine the structures and dynamics of such biomolecules in a membrane environment. While several biophysical techniques are used to obtain low-resolution information, solid-state NMR spectroscopy is one of the most powerful means for determining the structure and dynamics of membrane bound biomolecules such as antibacterial biomolecules and amyloidogenic proteins; unlike X-ray crystallography and solution NMR spectroscopy, applications of solid-state NMR spectroscopy are not limited by non-crystalline, non-soluble nature or molecular size of membrane-associated biomolecules. This review article focuses on the applications of solid-state NMR techniques to study a few selected antibacterial and amyloid peptides. Solid-state NMR studies revealing the membrane inserted bent α-helical structure associated with the hemolytic activity of bee venom melittin and the chemical shift oscillation analysis used to determine the transmembrane structure (with α-helix and 3 10 -helix in the N- and C-termini, respectively) of antibiotic peptide alamethicin are discussed in detail. Oligomerization of an amyloidogenic islet amyloid polypeptide (IAPP, or also known as amylin) resulting from its aggregation in a membrane environment, molecular interactions of the antifungal natural product amphotericin B with ergosterol in lipid bilayers, and the mechanism of lipid raft formation by sphingomyelin studied using solid state NMR methods are also discussed in this review article. This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A biophysical approach to menadione membrane interactions: relevance for menadione-induced mitochondria dysfunction and related deleterious/therapeutic effects.

    Science.gov (United States)

    Monteiro, João P; Martins, André F; Nunes, Cláudia; Morais, Catarina M; Lúcio, Marlene; Reis, Salette; Pinheiro, Teresa J T; Geraldes, Carlos F G C; Oliveira, Paulo J; Jurado, Amália S

    2013-08-01

    Menadione (MEN), a polycyclic aromatic ketone, was shown to promote cell injury by imposing massive oxidative stress and has been proposed as a promising chemotherapeutic agent for the treatment of cancer diseases. The mechanisms underlying MEN-induced mitochondrial dysfunction and cell death are not yet fully understood. In this work, a systematic study was performed to unveil the effects of MEN on membrane lipid organization, using models mimicking mitochondrial membranes and native mitochondrial membranes. MEN was found to readily incorporate in membrane systems composed of a single phospholipid (phosphatidylcholine) or the lipids dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine and tetraoleoylcardiolipin at 1:1:1 molar ratio, as well as in mitochondrial membranes. Increased permeability in both membrane models, monitored by calcein release, seemed to correlate with the extent of MEN incorporation into membranes. MEN perturbed the physical properties of vesicles composed of dipalmitoylphosphatidylcholine or dipalmitoylphosphatidylethanolamine plus tetraoleoylcardiolipin (at 7:3 molar ratio), as reflected by the downshift of the lipid phase transition temperature and the emergence of a new transition peak in the mixed lipid system, detected by DSC. (31)P NMR studies revealed that MEN favored the formation of non-lamellar structures. Also, quenching studies with the fluorescent probes DPH and TMA-DPH showed that MEN distributed across the bilayer thickness in both model and native mitochondrial membranes. MEN's ability to promote alterations of membrane lipid organization was related with its reported mitochondrial toxicity and promotion of apoptosis, predictably involved in its anti-carcinogenic activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Biotic games and cloud experimentation as novel media for biophysics education

    Science.gov (United States)

    Riedel-Kruse, Ingmar; Blikstein, Paulo

    2014-03-01

    First-hand, open-ended experimentation is key for effective formal and informal biophysics education. We developed, tested and assessed multiple new platforms that enable students and children to directly interact with and learn about microscopic biophysical processes: (1) Biotic games that enable local and online play using galvano- and photo-tactic stimulation of micro-swimmers, illustrating concepts such as biased random walks, Low Reynolds number hydrodynamics, and Brownian motion; (2) an undergraduate course where students learn optics, electronics, micro-fluidics, real time image analysis, and instrument control by building biotic games; and (3) a graduate class on the biophysics of multi-cellular systems that contains a cloud experimentation lab enabling students to execute open-ended chemotaxis experiments on slimemolds online, analyze their data, and build biophysical models. Our work aims to generate the equivalent excitement and educational impact for biophysics as robotics and video games have had for mechatronics and computer science, respectively. We also discuss how scaled-up cloud experimentation systems can support MOOCs with true lab components and life-science research in general.

  5. Ultra-high-density 3D DNA arrays within nanoporous biocompatible membranes for single-molecule-level detection and purification of circulating nucleic acids

    Czech Academy of Sciences Publication Activity Database

    Aramesh, M.; Shimoni, O.; Fox, K.; Karle, T.J.; Lohrmann, A.; Ostrikov, K.; Prawer, S.; Červenka, Jiří

    2015-01-01

    Roč. 7, č. 14 (2015), s. 5998-6006 ISSN 2040-3364 Institutional support: RVO:68378271 Keywords : Fourier-transform spectroscopy * alumina membranes * oligonucleotide hybridization Subject RIV: BO - Biophysics Impact factor: 7.760, year: 2015

  6. Preface: Special Topic on Single-Molecule Biophysics.

    Science.gov (United States)

    Makarov, Dmitrii E; Schuler, Benjamin

    2018-03-28

    Single-molecule measurements are now almost routinely used to study biological systems and processes. The scope of this special topic emphasizes the physics side of single-molecule observations, with the goal of highlighting new developments in physical techniques as well as conceptual insights that single-molecule measurements bring to biophysics. This issue also comprises recent advances in theoretical physical models of single-molecule phenomena, interpretation of single-molecule signals, and fundamental areas of statistical mechanics that are related to single-molecule observations. A particular goal is to illustrate the increasing synergy between theory, simulation, and experiment in single-molecule biophysics.

  7. 2. biophysical work meeting. Papers; 2. Biophysikalische Arbeitstagung; Vortraege

    Energy Technology Data Exchange (ETDEWEB)

    1992-11-01

    The report comprises 18 papers held at the 2nd Biophysical Work Meeting, 11 - 13 September 1991 in Schlema, Germany. The history of biophysics in Germany particularly of radiation biophysics and radon research, measurements of the radiation effects of radon and the derivation of limits, radon balneotherapy and consequences of uranium ore mining are dealt with. (orig.) [Deutsch] Der Report enthaelt 18 Vortraege, die auf der 2. Biophysikalischen Arbeitstagung in Schlema vom 11. bis 13. September 1991 gehalten wurden. Es werden die Geschichte der Biophysik in Deutschland, speziell der Strahlenbiophysik und Radonforschung, Messungen von Radon und seinen Folgeprodukten, Epidemiologie und Strahlenbiologie zur Bestimmung der Strahlenwirkung des Radons und die Ableitung entsprechender Grenzwerte, Radon-Balneotherapie und Folgen des Uranerzbergbaus behandelt. (orig.)

  8. α-Synuclein oligomers induced by docosahexaenoic acid affect membrane integrity.

    Directory of Open Access Journals (Sweden)

    Chiara Fecchio

    Full Text Available A key feature of Parkinson disease is the aggregation of α-synuclein and its intracellular deposition in fibrillar form. Increasing evidence suggests that the pathogenicity of α-synuclein is correlated with the activity of oligomers formed in the early stages of its aggregation process. Oligomers toxicity seems to be associated with both their ability to bind and affect the integrity of lipid membranes. Previously, we demonstrated that α-synuclein forms oligomeric species in the presence of docosahexaenoic acid and that these species are toxic to cells. Here we studied how interaction of these oligomers with membranes results in cell toxicity, using cellular membrane-mimetic and cell model systems. We found that α-synuclein oligomers are able to interact with large and small unilamellar negatively charged vesicles acquiring an increased amount of α-helical structure, which induces small molecules release. We explored the possibility that oligomers effects on membranes could be due to pore formation, to a detergent-like effect or to fibril growth on the membrane. Our biophysical and cellular findings are consistent with a model where α-synuclein oligomers are embedded into the lipid bilayer causing transient alteration of membrane permeability.

  9. THE NANOSTRUCTURE OF ERYTHROCYTE MEMBRANES UNDER BLOOD INTOXICATION: AN ATOMIC FORCE MICROSCOPY STUDY

    Directory of Open Access Journals (Sweden)

    V. A. Sergunova

    2016-01-01

    Full Text Available Background: The effects of toxins on nanostructure of blood cells are one of the key problems of biophysics and medicine. Erythrocyte morphology and membrane structure are recognized as the main parameters of blood quality. Therefore, analysis of membrane defects under toxin effects seems an urgent issue. Aim: To identify characteristic features and patterns of changes in membrane nanostructure under hemin intoxication and during extended storage of erythrocyte suspension. Materials and methods: The study was done in vitro in human whole blood with addition of hemin, аnd in erythrocyte suspension with a CPD blood preservative stored at 4 °С for 30 days. The nanostructure of erythrocyte membrane was assessed by atomic force microscopy. Results: Characteristic size of space periods between “granules” was from 120 to 200 nm. “Granule” numbers within a topological defect varied from 4 to 5 and to several dozens. Such domains arose virtually on all cells in erythrocyte suspension, as well as after hemin addition to the blood. An increase in hemin intoxication and an increase in a storage time were associated by increases in echinocyte numbers that subsequently transformed into spherical echinocytes. Both under hemin and during the storage of erythrocyte suspension for 9 to 12 days, a specific abnormality in nanostructure of erythrocyte membrane was observed: structural clusters, i.e., domains with granular structure, were formed. Conclusion: The experiments showed that both hemin and oxidative processes in the blood can specifically affect the nanostructure of erythrocyte membranes with formation of domains on their surface. The specific size of granular structures in the domains is from 100 to 200 nm that coincides with a  specific size of spectrin matrix. These results can be used in basic and applied medicine, in blood transfusion, for the analysis of a toxin effects in the human body. The biophysical mechanisms of domain

  10. Mass spectrometry in structural biology and biophysics architecture, dynamics, and interaction of biomolecules

    CERN Document Server

    Kaltashov, Igor A; Desiderio, Dominic M; Nibbering, Nico M

    2012-01-01

    The definitive guide to mass spectrometry techniques in biology and biophysics The use of mass spectrometry (MS) to study the architecture and dynamics of proteins is increasingly common within the biophysical community, and Mass Spectrometry in Structural Biology and Biophysics: Architecture, Dynamics, and Interaction of Biomolecules, Second Edition provides readers with detailed, systematic coverage of the current state of the art. Offering an unrivalled overview of modern MS-based armamentarium that can be used to solve the most challenging problems in biophysics, structural biol

  11. Comparison of biophysical factors influencing on emphysema quantification with low-dose CT

    Science.gov (United States)

    Heo, Chang Yong; Kim, Jong Hyo

    2014-03-01

    Emphysema Index(EI) measurements in MDCT is known to be influenced by various biophysical factors such as total lung volume, and body size. We investigated the association of the four biophysical factors with emphysema index in low-dose MDCT. In particular, we attempted to identify a potentially stronger biophysical factor than total lung volume. A total of 400 low-dose MDCT volumes taken at 120kVp, 40mAs, 1mm thickness, and B30f reconstruction kernel were used. The lungs, airways, and pulmonary vessels were automatically segmented, and two Emphysema Indices, relative area below -950HU(RA950) and 15th percentile(Perc15), were extracted from the segmented lungs. The biophysical factors such as total lung volume(TLV), mode of lung attenuation(ModLA), effective body diameter(EBD), and the water equivalent body diameter(WBD) were estimated from the segmented lung and body area. The association of biophysical factors with emphysema indices were evaluated by correlation coefficients. The mean emphysema indices were 8.3±5.5(%) in RA950, and -930±18(HU) in Perc15. The estimates of biophysical factors were 4.7±1.0(L) in TLV, -901±21(HU) in ModLA, 26.9±2.2(cm) in EBD, and 25.9±2.6(cm) in WBD. The correlation coefficients of biophysical factors with RA950 were 0.73 in TLV, 0.94 in ModLA, 0.31 in EBD, and 0.18 WBD, the ones with Perc15 were 0.74 in TLV, 0.98 in ModLA, 0.29 in EBD, and 0.15 WBD. Study results revealed that two biophysical factors, TLV and ModLA, mostly affects the emphysema indices. In particular, the ModLA exhibited strongest correlation of 0.98 with Perc15, which indicating the ModLA is the most significant confounding biophysical factor in emphysema indices measurement.

  12. Biophysics of Human Hair Structural, Nanomechanical, and Nanotribological Studies

    CERN Document Server

    Bhushan, Bharat

    2010-01-01

    This book presents the biophysics of hair. It deals with the structure of hair, its mechanical properties, the nanomechanical characterization, tensile deformation, tribological characterization, the thickness distribution and binding interactions on hair surface. Another important topic of the book is the health of hair, human hair and skin, hair care, cleaning and conditioning treatments and damaging processes. It is the first book on the biophysical properties of hair.

  13. Applications of synchrotron radiation in Biophysics

    International Nuclear Information System (INIS)

    Bemski, G.

    1983-01-01

    A short introduction to the generation of the synchrotron radiation is made. Following, the applications of such a radiation in biophysics with emphasis to the study of the hemoglobin molecule are presented. (L.C.) [pt

  14. A subsequent closed-form description of propagated signaling phenomena in the membrane of an axon

    Energy Technology Data Exchange (ETDEWEB)

    Melendy, Robert F., E-mail: rfmelendy@liberty.edu [School of Engineering and Computational Science, Liberty University, Lynchburg, Virginia, 24515 (United States)

    2016-05-15

    I recently introduced a closed-form description of propagated signaling phenomena in the membrane of an axon [R.F. Melendy, Journal of Applied Physics 118, 244701 (2015)]. Those results demonstrate how intracellular conductance, the thermodynamics of magnetization, and current modulation, function together in generating an action potential in a unified, closed-form description. At present, I report on a subsequent closed-form model that unifies intracellular conductance and the thermodynamics of magnetization, with the membrane electric field, E{sub m}. It’s anticipated this work will compel researchers in biophysics, physical biology, and the computational neurosciences, to probe deeper into the classical and quantum features of membrane magnetization and signaling, informed by the computational features of this subsequent model.

  15. A subsequent closed-form description of propagated signaling phenomena in the membrane of an axon

    Science.gov (United States)

    Melendy, Robert. F.

    2016-05-01

    I recently introduced a closed-form description of propagated signaling phenomena in the membrane of an axon [R.F. Melendy, Journal of Applied Physics 118, 244701 (2015)]. Those results demonstrate how intracellular conductance, the thermodynamics of magnetization, and current modulation, function together in generating an action potential in a unified, closed-form description. At present, I report on a subsequent closed-form model that unifies intracellular conductance and the thermodynamics of magnetization, with the membrane electric field, Em. It's anticipated this work will compel researchers in biophysics, physical biology, and the computational neurosciences, to probe deeper into the classical and quantum features of membrane magnetization and signaling, informed by the computational features of this subsequent model.

  16. Monitoring voltage-sensitive membrane impedance change using radio frequency interrogation.

    Science.gov (United States)

    Dharia, Sameera; Rabbitt, Richard D

    2010-01-01

    Here we present a new technique to monitor dynamic conformational changes in voltage-sensitive membrane-bound proteins using radio frequency (RF) impedance measurements. Xenopus oocytes were transfected to express ShakerB-IR K(+) ion channels, and step changes in membrane potential were applied using two-electrode voltage clamp (TEVC). Simultaneously, bipolar extracellular electrodes were used to measure the RF electrical impedance across the cell (300 kHz - 1 MHz). RF current will either pass through the media, around the cell, or displace charge across the cell membrane. The change in displacement current in the cell membrane during voltage clamp resulted in measurable RF impedance change. RF impedance change during DC membrane depolarization was significantly greater in ShakerB-IR expressing oocytes than in endogenous controls at 300 kHz, 500 kHz and, to a lesser extent, 1 MHz. Since the RF were too high to modulate ShakerB-IR protein conformational state (e.g. open channel probability), impedance changes are interpreted as reflections of voltage-dependent protein conformation and associated biophysics such as ion-channel dipole interactions, fluctuations in bound water, or charged lipid head-group rotations.

  17. Biological Membrane Ion Channels Dynamics, Structure, and Applications

    CERN Document Server

    Chung, Shin-Ho; Krishnamurthy, Vikram

    2007-01-01

    Ion channels are biological nanotubes that are formed by membrane proteins. Because ion channels regulate all electrical activities in living cells, understanding their mechanisms at a molecular level is a fundamental problem in biology. This book deals with recent breakthroughs in ion-channel research that have been brought about by the combined effort of experimental biophysicists and computational physicists, who together are beginning to unravel the story of these exquisitely designed biomolecules. With chapters by leading experts, the book is aimed at researchers in nanodevices and biosensors, as well as advanced undergraduate and graduate students in biology and the physical sciences. Key Features Presents the latest information on the molecular mechanisms of ion permeation through membrane ion channels Uses schematic diagrams to illustrate important concepts in biophysics Written by leading researchers in the area of ion channel investigations

  18. Structural studies of the lipid membranes at the Siberia-2 synchrotron radiation source

    International Nuclear Information System (INIS)

    Kiselev, M. A.; Ermakova, E. V.; Ryabova, N. Yu.; Nayda, O. V.; Zabelin, A. V.; Pogorely, D. K.; Korneev, V. N.; Balagurov, A. M.

    2010-01-01

    Lipid membranes are a subject of contemporary interdisciplinary studies at the junction of biology, biophysics, pharmacology, and bionanotechnology. The results of the structural studies of several types of lipid membranes by the lamellar and lateral diffraction of X-ray synchrotron radiation are presented. The experiments were performed at the Mediana and DICSI stations of the Siberia-2 synchrotron radiation source at the Russian Research Center Kurchatov Institute. The data obtained are compared with the results of studying lipid membranes at the small-angle scattering beamlines D22 and D24 at LURE (France) and at the A2 beamline at DESY (Germany). The parameters of the DICSI station are shown to meet the basic requirements for the structural study of lipid systems, which are of fundamental and applied interest.

  19. Biophysical aspects of photodynamic therapy.

    Science.gov (United States)

    Juzeniene, Asta; Nielsen, Kristian Pagh; Moan, Johan

    2006-01-01

    Over the last three decades photodynamic therapy (PDT) has been developed to a useful clinical tool, a viable alternative in the treatment of cancer and other diseases. Several disciplines have contributed to this development: chemistry in the development of new photosensitizing agents, biology in the elucidation of cellular processes involved in PDT, pharmacology and physiology in identifying the mechanisms of distribution of photosensitizers in an organism, and, last but not least, physics in the development of better light sources, dosimetric concepts and construction of imaging devices, optical sensors and spectroscopic methods for determining sensitizer concentrations in different tissues. Physics and biophysics have also helped to focus on the role of pH for sensitizer accumulation, dose rate effects, oxygen depletion, temperature, and optical penetration of light of different wavelengths into various types of tissue. These are all important parameters for optimally effective PDT. The present review will give a brief, physically based, overview of PDT and then discuss some of the main biophysical aspects of this therapeutic modality.

  20. Building biophysics in mid-century China: the University of Science and Technology of China.

    Science.gov (United States)

    Luk, Yi Lai Christine

    2015-01-01

    Biophysics has been either an independent discipline or an element of another discipline in the United States, but it has always been recognized as a stand-alone discipline in the People's Republic of China (PRC) since 1949. To inquire into this apparent divergence, this paper investigates the formational history of biophysics in China by examining the early institutional history of one of the best-known and prestigious science and technology universities in the PRC, the University of Science and Technology of China (USTC). By showing how the university and its biophysics program co-evolved with national priorities from the school's founding in 1958 to the eve of the Cultural Revolution in 1966, the purpose of this paper is to assess the development of a scientific discipline in the context of national demands and institutional politics. Specific materials for analysis include the school's admission policies, curricula, students' dissertations, and research program. To further contextualize the institutional setting of Chinese biophysics, this paper begins with a general history of proto-biophysical institutions in China during the Nationalist-Communist transitional years. This paper could be of interest to historians wanting to know more about the origin of the biophysics profession in China, and in particular how research areas that constitute biophysics changed in tandem with socio-political contingencies.

  1. Biophysical aspects of cancer - Electromagnetic mechanism

    Czech Academy of Sciences Publication Activity Database

    Pokorný, Jiří; Hašek, Jiří; Vaniš, Jan; Jelínek, František

    2008-01-01

    Roč. 46, č. 5 (2008), s. 310-321 ISSN 0019-5189 Institutional research plan: CEZ:AV0Z20670512; CEZ:AV0Z50200510 Keywords : Electromagnetic Fields * Biophysics * Cancer Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 0.599, year: 2008

  2. The computational route from bilayer membranes to vesicle fusion

    International Nuclear Information System (INIS)

    Shillcock, Julian C; Lipowsky, Reinhard

    2006-01-01

    Biological membranes are examples of 'smart' materials whose properties and behaviour emerge from the propagation across many scales of the molecular characteristics of their constituents. Artificial smart materials, such as drug delivery vehicles and biosensors, often rely on modifying naturally occurring soft matter, such as polymers and lipid vesicles, so that they possess useful behaviour. However, the complexity of natural membranes, both in their static properties, exemplified in their phase behaviour, and in their dynamic properties, as in the kinetics of their formation and interactions, hinders their rational modification. Mesoscopic simulations, such as dissipative particle dynamics (DPD), allow in silico experiments to be easily and cheaply performed on complex, soft materials requiring as input only the molecular structure of the constituents at a coarse-grained level. They can therefore act as a guide to experimenters prior to performing costly assays. Additionally, mesoscopic simulations provide the only currently feasible window on the length- and timescales relevant to important biophysical processes such as vesicle fusion. We review here the development of computational models of bilayer membranes, and in particular the use of mesoscopic simulations to follow the molecular rearrangements that occur during membrane fusion

  3. Membranolytic Activity of Bile Salts: Influence of Biological Membrane Properties and Composition

    Directory of Open Access Journals (Sweden)

    Alfred Blume

    2007-10-01

    Full Text Available The two main steps of the membranolytic activity of detergents: 1 the partitioning of detergent molecules in the membrane and 2 the solubilisation of the membrane are systematically investigated. The interactions of two bile salt molecules, sodium cholate (NaC and sodium deoxycholate (NaDC with biological phospholipid model membranes are considered. The membranolytic activity is analysed as a function of the hydrophobicity of the bile salt, ionic strength, temperature, membrane phase properties, membrane surface charge and composition of the acyl chains of the lipids. The results are derived from calorimetric measurements (ITC, isothermal titration calorimetry. A thermodynamic model is described, taking into consideration electrostatic interactions, which is used for the calculation of the partition coefficient as well as to derive the complete thermodynamic parameters describing the interaction of detergents with biological membranes (change in enthalpy, change in free energy, change in entropy etc. The solubilisation properties are described in a so-called vesicle-to-micelle phase transition diagram. The obtained results are supplemented and confirmed by data obtained from other biophysical techniques (DSC differential scanning calorimetry, DLS dynamic light scattering, SANS small angle neutron scattering.

  4. Uncovering homo-and hetero-interactions on the cell membrane using single particle tracking approaches

    International Nuclear Information System (INIS)

    Torreno-Pina, Juan A; Manzo, Carlo; Garcia-Parajo, Maria F

    2016-01-01

    The plasma membrane of eukaryotic cells is responsible for a myriad of functions that regulate cell physiology and plays a crucial role in a multitude of processes that include adhesion, migration, signaling recognition and cell–cell communication. This is accomplished by specific interactions between different membrane components such as lipids and proteins on the lipid bilayer but also through interactions with the underlying cortical actin cytoskeleton on the intracellular side and the glycocalyx matrix in close proximity to the extracellular side. Advanced biophysical techniques, including single particle tracking (SPT) have revealed that the lateral diffusion of molecular components on the plasma membrane represents a landmark manifestation of such interactions. Indeed, by studying changes in the diffusivity of individual membrane molecules, including sub-diffusion, confined diffusion and/or transient arrest of molecules in membrane compartments, it has been possible to gain insight on the nature of molecular interactions and to infer on its functional role for cell response. In this review, we will revise some exciting results where SPT has been crucial to reveal homo- and hetero-interactions on the cell membrane. (paper)

  5. Silicon-on-insulator based nanopore cavity arrays for lipid membrane investigation.

    Science.gov (United States)

    Buchholz, K; Tinazli, A; Kleefen, A; Dorfner, D; Pedone, D; Rant, U; Tampé, R; Abstreiter, G; Tornow, M

    2008-11-05

    We present the fabrication and characterization of nanopore microcavities for the investigation of transport processes in suspended lipid membranes. The cavities are situated below the surface of silicon-on-insulator (SOI) substrates. Single cavities and large area arrays were prepared using high resolution electron-beam lithography in combination with reactive ion etching (RIE) and wet chemical sacrificial underetching. The locally separated compartments have a circular shape and allow the enclosure of picoliter volume aqueous solutions. They are sealed at their top by a 250 nm thin Si membrane featuring pores with diameters from 2 µm down to 220 nm. The Si surface exhibits excellent smoothness and homogeneity as verified by AFM analysis. As biophysical test system we deposited lipid membranes by vesicle fusion, and demonstrated their fluid-like properties by fluorescence recovery after photobleaching. As clearly indicated by AFM measurements in aqueous buffer solution, intact lipid membranes successfully spanned the pores. The nanopore cavity arrays have potential applications in diagnostics and pharmaceutical research on transmembrane proteins.

  6. A dataset mapping the potential biophysical effects of vegetation cover change

    Science.gov (United States)

    Duveiller, Gregory; Hooker, Josh; Cescatti, Alessandro

    2018-02-01

    Changing the vegetation cover of the Earth has impacts on the biophysical properties of the surface and ultimately on the local climate. Depending on the specific type of vegetation change and on the background climate, the resulting competing biophysical processes can have a net warming or cooling effect, which can further vary both spatially and seasonally. Due to uncertain climate impacts and the lack of robust observations, biophysical effects are not yet considered in land-based climate policies. Here we present a dataset based on satellite remote sensing observations that provides the potential changes i) of the full surface energy balance, ii) at global scale, and iii) for multiple vegetation transitions, as would now be required for the comprehensive evaluation of land based mitigation plans. We anticipate that this dataset will provide valuable information to benchmark Earth system models, to assess future scenarios of land cover change and to develop the monitoring, reporting and verification guidelines required for the implementation of mitigation plans that account for biophysical land processes.

  7. Bacterial Reaction Centers Purified with Styrene Maleic Acid Copolymer Retain Native Membrane Functional Properties and Display Enhanced Stability**

    Science.gov (United States)

    Swainsbury, David J K; Scheidelaar, Stefan; van Grondelle, Rienk; Killian, J Antoinette; Jones, Michael R

    2014-01-01

    Integral membrane proteins often present daunting challenges for biophysical characterization, a fundamental issue being how to select a surfactant that will optimally preserve the individual structure and functional properties of a given membrane protein. Bacterial reaction centers offer a rare opportunity to compare the properties of an integral membrane protein in different artificial lipid/surfactant environments with those in the native bilayer. Here, we demonstrate that reaction centers purified using a styrene maleic acid copolymer remain associated with a complement of native lipids and do not display the modified functional properties that typically result from detergent solubilization. Direct comparisons show that reaction centers are more stable in this copolymer/lipid environment than in a detergent micelle or even in the native membrane, suggesting a promising new route to exploitation of such photovoltaic integral membrane proteins in device applications. PMID:25212490

  8. A mathematical approach to protein biophysics

    CERN Document Server

    Scott, L Ridgway

    2017-01-01

    This book explores quantitative aspects of protein biophysics and attempts to delineate certain rules of molecular behavior that make atomic scale objects behave in a digital way.  This book will help readers to understand how certain biological systems involving proteins function as digital information systems despite the fact that underlying processes are analog in nature. The in-depth explanation of proteins from a quantitative point of view and the variety of level of exercises (including physical experiments) at the end of each chapter will appeal to graduate and senior undergraduate students in mathematics, computer science, mechanical engineering, and physics, wanting to learn about the biophysics of proteins.  L. Ridgway Scott has been Professor of Computer Science and of Mathematics at the University of Chicago since 1998, and the Louis Block Professor since 2001.  He obtained a B.S. degree (Magna Cum Laude) from Tulane University in 1969 and a PhD degree in Mathematics from the Massachusetts Ins...

  9. Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins.

    Science.gov (United States)

    Chae, Pil Seok; Rasmussen, Søren G F; Rana, Rohini R; Gotfryd, Kamil; Chandra, Richa; Goren, Michael A; Kruse, Andrew C; Nurva, Shailika; Loland, Claus J; Pierre, Yves; Drew, David; Popot, Jean-Luc; Picot, Daniel; Fox, Brian G; Guan, Lan; Gether, Ulrik; Byrne, Bernadette; Kobilka, Brian; Gellman, Samuel H

    2010-12-01

    The understanding of integral membrane protein (IMP) structure and function is hampered by the difficulty of handling these proteins. Aqueous solubilization, necessary for many types of biophysical analysis, generally requires a detergent to shield the large lipophilic surfaces of native IMPs. Many proteins remain difficult to study owing to a lack of suitable detergents. We introduce a class of amphiphiles, each built around a central quaternary carbon atom derived from neopentyl glycol, with hydrophilic groups derived from maltose. Representatives of this maltose-neopentyl glycol (MNG) amphiphile family show favorable behavior relative to conventional detergents, as manifested in multiple membrane protein systems, leading to enhanced structural stability and successful crystallization. MNG amphiphiles are promising tools for membrane protein science because of the ease with which they may be prepared and the facility with which their structures may be varied.

  10. Institute of Biochemistry and Biophysics. Research Report 1996-1997

    International Nuclear Information System (INIS)

    1998-01-01

    Scientific interests of the Institute of Biochemistry and Biophysics of the Polish Academy of Sciences have evolved from classical biochemistry, biophysics and physiological chemistry to up-to-date molecular biology. Research interests are focussed on replication, mutagenesis and repair of DNA; regulation of gene expression at various levels; biosynthesis and post-translational modifications of proteins; gene sequencing and functional analysis of open reading frames; structure, function and regulation of enzymes; conformation of proteins and peptides; modelling of structures and prediction of functions of proteins; mechanisms of electron transfer in polypeptides

  11. Institute of Biochemistry and Biophysics. Research Report 1996-1997

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-07-01

    Scientific interests of the Institute of Biochemistry and Biophysics of the Polish Academy of Sciences have evolved from classical biochemistry, biophysics and physiological chemistry to up-to-date molecular biology. Research interests are focussed on replication, mutagenesis and repair of DNA; regulation of gene expression at various levels; biosynthesis and post-translational modifications of proteins; gene sequencing and functional analysis of open reading frames; structure, function and regulation of enzymes; conformation of proteins and peptides; modelling of structures and prediction of functions of proteins; mechanisms of electron transfer in polypeptides.

  12. Trehalose: a biophysics approach to modulate the inflammatory response during endotoxic shock.

    Science.gov (United States)

    Minutoli, Letteria; Altavilla, Domenica; Bitto, Alessandra; Polito, Francesca; Bellocco, Ersilia; Laganà, Giuseppina; Fiumara, Tiziana; Magazù, Salvatore; Migliardo, Federica; Venuti, Francesco Saverio; Squadrito, Francesco

    2008-07-28

    We evaluated the effects of trehalose against endotoxic shock, a condition in which the loss of bio-membrane integrity plays a pivotal role. In addition we performed a biophysics experiment by quasi elastic neutron scattering (QENS) study, to investigate whether the membrane stability effect of trehalose might be correlated with its high capability to switch-off the water diffusive dynamics and, hence, the kinetic mechanisms of interaction. Endotoxic shock was induced in male rats by a single injection of Salmonella enteritidis lipopolysaccharide (LPS; 20 mg/kg/i.p.). Thirty minutes before and 2 h after LPS injection, the animals were randomized to receive vehicle (1 ml/kg/i.p. 0.9%NaCl), sucrose (1 g/kg/i.p.) or trehalose (1 g/kg/i.p.). Mean arterial blood pressure, nuclear factor-kappaB (NF-kappaB) binding activity, Ikappa-Balpha and toll-like receptor-4 (TLR-4) activation were evaluated in both liver and lung. Plasmatic tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) and malondialdehyde (MDA) were also investigated. We studied liver injury by means of blood alanine aminotransferase activity (ALT); inducible nitric oxide synthase (iNOS) expression, myeloperoxidase (MPO) activity and tissue edema evaluation. Lung injury was investigated by means of tissue monocyte chemoattractant protein-1 (MCP-1) levels, MPO activity, iNOS expression and edema formation. Trehalose reduced hypotension, NF-kappaB binding activity, IkappaBalpha protein loss and TLR-4 activation. In addition trehalose reduced TNF-alpha, IL-1, IL-6 and MDA levels. Trehalose also blunted liver and lung injury. QENS measurements showed also that trehalose possesses a high "switching off" capability. Sucrose did not modify endotoxic shock-induced sequelae. Trehalose blocked the inflammatory cascade triggered by endotoxin shock, stabilizing the bio-membranes and switching off the water diffusive dynamics.

  13. Biophysical Influence of Airborne Carbon Nanomaterials on Natural Pulmonary Surfactant

    OpenAIRE

    Valle, Russell P.; Wu, Tony; Zuo, Yi Y.

    2015-01-01

    Inhalation of nanoparticles (NP), including lightweight airborne carbonaceous nanomaterials (CNM), poses a direct and systemic health threat to those who handle them. Inhaled NP penetrate deep pulmonary structures in which they first interact with the pulmonary surfactant (PS) lining at the alveolar air–water interface. In spite of many research efforts, there is a gap of knowledge between in vitro biophysical study and in vivo inhalation toxicology since all existing biophysical models handl...

  14. Research Institute for Medical Biophysics

    International Nuclear Information System (INIS)

    Wynchank, S.

    1989-01-01

    The effects of ionising and non-ionising radiation on rodent tumours and normal tissue were studied in terms of cellular repair and the relevant biochemical and biophysical changes following radiation. Rodent tumours investigated in vivo were the CaNT adenocarcinoma and a chemically induced transplantable rhabdomyosarcoma. Radiations used were 100KVp of X-Rays, neutron beams, various magnetic fields, and microwave radiation of 2450MHz. The biochemical parameters measured were, inter alia, levels of adenosine-5'-triphoshate (ATP) and the specific activity of hexokinase (HK). Metabolic changes in ATP levels and the activity of HK were observed in tumour and normal tissues following ionising and non-ionising radiation in normoxia and hypoxia. The observation that the effect of radiation and chemotherapeutic treatment of some tumours may be size dependent can possibly now be explained by the variation of ATP content with tumour size. The enhanced tumour HK specific activity implies increased metabolism, possibly a consequence of cellular requirements to maintain homeostasis during repair processes. Other research projects of the Research Institute for Medical Biophysics involved, inter alia, gastroesophageal scintigraphies to evaluate the results of new forms of therapy. 1 ill

  15. Effects of pressure and electrical charge on macromolecular transport across bovine lens basement membrane.

    Science.gov (United States)

    Ferrell, Nicholas; Cameron, Kathleen O; Groszek, Joseph J; Hofmann, Christina L; Li, Lingyan; Smith, Ross A; Bian, Aihua; Shintani, Ayumi; Zydney, Andrew L; Fissell, William H

    2013-04-02

    Molecular transport through the basement membrane is important for a number of physiological functions, and dysregulation of basement membrane architecture can have serious pathological consequences. The structure-function relationships that govern molecular transport in basement membranes are not fully understood. The basement membrane from the lens capsule of the eye is a collagen IV-rich matrix that can easily be extracted and manipulated in vitro. As such, it provides a convenient model for studying the functional relationships that govern molecular transport in basement membranes. Here we investigate the effects of increased transmembrane pressure and solute electrical charge on the transport properties of the lens basement membrane (LBM) from the bovine eye. Pressure-permeability relationships in LBM transport were governed primarily by changes in diffusive and convective contributions to solute flux and not by pressure-dependent changes in intrinsic membrane properties. The solute electrical charge had a minimal but statistically significant effect on solute transport through the LBM that was opposite of the expected electrokinetic behavior. The observed transport characteristics of the LBM are discussed in the context of established membrane transport modeling and previous work on the effects of pressure and electrical charge in other basement membrane systems. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  16. Biophysics of Hair Cell Sensory Systems

    NARCIS (Netherlands)

    Duifhuis, Hendrikus; Horst, Johannes; van Dijk, Pim; van Netten, Sietse

    1993-01-01

    The last decade revealed to auditory researchers that hair cells can not only detect and process mechanical energy, but are also able to produce it. Thanks to the active hair cell, ears can produce otoacoustic emissions. This book gives the newest insights into the biophysics and physiology of

  17. Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins

    OpenAIRE

    Chae, Pil Seok; Rasmussen, Søren G. F.; Rana, Rohini; Gotfryd, Kamil; Chandra, Richa; Goren, Michael A.; Kruse, Andrew C.; Nurva, Shailika; Loland, Claus J.; Pierre, Yves; Drew, David; Popot, Jean-Luc; Picot, Daniel; Fox, Brian G.; Guan, Lan

    2010-01-01

    The understanding of integral membrane protein (IMP) structure and function is hampered by the difficulty of handling these proteins. Aqueous solubilization, necessary for many types of biophysical analysis, generally requires a detergent to shield the large lipophilic surfaces displayed by native IMPs. Many proteins remain difficult to study owing to a lack of suitable detergents. We introduce a class of amphiphiles, each of which is built around a central quaternary carbon atom derived from...

  18. The role of cholesterol in the association of endoplasmic reticulum membranes with mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, Michiko [Cellular Stress Signaling Unit, Integrative Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224 (United States); Hayashi, Teruo, E-mail: thayashi@mail.nih.gov [Cellular Stress Signaling Unit, Integrative Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224 (United States); Su, Tsung-Ping, E-mail: tsu@intra.nida.nih.gov [Cellular Pathobiology Section, Integrative Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224 (United States)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer The endoplasmic reticulum subdomain termed MAM associates with mitochondria. Black-Right-Pointing-Pointer The biophysical role of lipids in the MAM-mitochondria association is unknown. Black-Right-Pointing-Pointer The in vitro membrane association assay was used to examine the role of lipids. Black-Right-Pointing-Pointer Cholesterol was found to negatively regulate the association. -- Abstract: The unique endoplasmic reticulum (ER) subdomain termed the mitochondria-associated ER membrane (MAM) engages the physical connection between the ER and the mitochondrial outer membrane and plays a role in regulating IP{sub 3} receptor-mediated Ca{sup 2+} influx and the phospholipid transport between the two organelles. The MAM contains certain signaling and membrane-tethering proteins but also lipids including cholesterol. The biophysical role of lipids at the MAM, specifically in the physical interaction between the MAM of the ER and mitochondria, remains not totally clarified. Here we employed the in vitro membrane association assay to investigate the role of cholesterol in the association between MAMs and mitochondria. The purified MAMs and mitochondria were mixed in vitro in a test tube and then the physical association of the two subcellular organelles was quantified indirectly by measuring the presence of the MAM-specific protein sigma-1 receptors in the mitochondria fraction. Purified MAMs contained free cholesterol approximately 7 times higher than that in microsomes. We found that depletion of cholesterol in MAMs with methyl-{beta}-cyclodextrin (M{beta}C) significantly increases the association between MAMs and mitochondria, whereas M{beta}C saturated with cholesterol does not change the association. {sup 14}C-Serine pulse-labeling demonstrated that the treatment of living cells with M{beta}C decreases the level of de novo synthesized {sup 14}C-phosphatidylserine (PtSer) and concomitantly increases greatly the synthesis of

  19. The role of cholesterol in the association of endoplasmic reticulum membranes with mitochondria

    International Nuclear Information System (INIS)

    Fujimoto, Michiko; Hayashi, Teruo; Su, Tsung-Ping

    2012-01-01

    Highlights: ► The endoplasmic reticulum subdomain termed MAM associates with mitochondria. ► The biophysical role of lipids in the MAM–mitochondria association is unknown. ► The in vitro membrane association assay was used to examine the role of lipids. ► Cholesterol was found to negatively regulate the association. -- Abstract: The unique endoplasmic reticulum (ER) subdomain termed the mitochondria-associated ER membrane (MAM) engages the physical connection between the ER and the mitochondrial outer membrane and plays a role in regulating IP 3 receptor-mediated Ca 2+ influx and the phospholipid transport between the two organelles. The MAM contains certain signaling and membrane-tethering proteins but also lipids including cholesterol. The biophysical role of lipids at the MAM, specifically in the physical interaction between the MAM of the ER and mitochondria, remains not totally clarified. Here we employed the in vitro membrane association assay to investigate the role of cholesterol in the association between MAMs and mitochondria. The purified MAMs and mitochondria were mixed in vitro in a test tube and then the physical association of the two subcellular organelles was quantified indirectly by measuring the presence of the MAM-specific protein sigma-1 receptors in the mitochondria fraction. Purified MAMs contained free cholesterol approximately 7 times higher than that in microsomes. We found that depletion of cholesterol in MAMs with methyl-β-cyclodextrin (MβC) significantly increases the association between MAMs and mitochondria, whereas MβC saturated with cholesterol does not change the association. 14 C-Serine pulse-labeling demonstrated that the treatment of living cells with MβC decreases the level of de novo synthesized 14 C-phosphatidylserine (PtSer) and concomitantly increases greatly the synthesis of 14 C-phosphatidylethanolamine (PtEt). Apparently, cholesterol depletion increased the PtSer transport from MAMs to mitochondria. Our

  20. Replacing natural wetlands with stormwater management facilities: Biophysical and perceived social values.

    Science.gov (United States)

    Rooney, R C; Foote, L; Krogman, N; Pattison, J K; Wilson, M J; Bayley, S E

    2015-04-15

    Urban expansion replaces wetlands of natural origin with artificial stormwater management facilities. The literature suggests that efforts to mimic natural wetlands in the design of stormwater facilities can expand the provision of ecosystem services. Policy developments seek to capitalize on these improvements, encouraging developers to build stormwater wetlands in place of stormwater ponds; however, few have compared the biophysical values and social perceptions of these created wetlands to those of the natural wetlands they are replacing. We compared four types of wetlands: natural references sites, natural wetlands impacted by agriculture, created stormwater wetlands, and created stormwater ponds. We anticipated that they would exhibit a gradient in biodiversity, ecological integrity, chemical and hydrologic stress. We further anticipated that perceived values would mirror measured biophysical values. We found higher biophysical values associated with wetlands of natural origin (both reference and agriculturally impacted). The biophysical values of stormwater wetlands and stormwater ponds were lower and indistinguishable from one another. The perceived wetland values assessed by the public differed from the observed biophysical values. This has important policy implications, as the public are not likely to perceive the loss of values associated with the replacement of natural wetlands with created stormwater management facilities. We conclude that 1) agriculturally impacted wetlands provide biophysical values equivalent to those of natural wetlands, meaning that land use alone is not a great predictor of wetland value; 2) stormwater wetlands are not a substantive improvement over stormwater ponds, relative to wetlands of natural origin; 3) stormwater wetlands are poor mimics of natural wetlands, likely due to fundamental distinctions in terms of basin morphology, temporal variation in hydrology, ground water connectivity, and landscape position; 4) these

  1. Polish Academy of Sciences Institute of Biochemistry and Biophysics research report 1994-1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    Scientific interests of Institute of Biochemistry and Biophysics Polish Academy of Sciences are focused on DNA replication and repair, gene expression, gene sequencing and molecular biophysics. The work reviews research projects of the Institute in 1994-1995.

  2. Polish Academy of Sciences Institute of Biochemistry and Biophysics research report 1994-1995

    International Nuclear Information System (INIS)

    1996-01-01

    Scientific interests of Institute of Biochemistry and Biophysics Polish Academy of Sciences are focused on DNA replication and repair, gene expression, gene sequencing and molecular biophysics. The work reviews research projects of the Institute in 1994-1995

  3. Polish Academy of Sciences Institute of Biochemistry and Biophysics research report 1994-1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    Scientific interests of Institute of Biochemistry and Biophysics Polish Academy of Sciences are focused on DNA replication and repair, gene expression, gene sequencing and molecular biophysics. The work reviews research projects of the Institute in 1994-1995.

  4. Surface-enhanced Raman scattering: a new optical probe in molecular biophysics and biomedicine

    DEFF Research Database (Denmark)

    Kneipp, J.; Wittig, B.; Bohr, Henrik

    2010-01-01

    Sensitive and detailed molecular structural information plays an increasing role in molecular biophysics and molecular medicine. Therefore, vibrational spectroscopic techniques, such as Raman scattering, which provide high structural information content are of growing interest in biophysical and ...

  5. Remodeling of the postsynaptic plasma membrane during neural development.

    Science.gov (United States)

    Tulodziecka, Karolina; Diaz-Rohrer, Barbara B; Farley, Madeline M; Chan, Robin B; Di Paolo, Gilbert; Levental, Kandice R; Waxham, M Neal; Levental, Ilya

    2016-11-07

    Neuronal synapses are the fundamental units of neural signal transduction and must maintain exquisite signal fidelity while also accommodating the plasticity that underlies learning and development. To achieve these goals, the molecular composition and spatial organization of synaptic terminals must be tightly regulated; however, little is known about the regulation of lipid composition and organization in synaptic membranes. Here we quantify the comprehensive lipidome of rat synaptic membranes during postnatal development and observe dramatic developmental lipidomic remodeling during the first 60 postnatal days, including progressive accumulation of cholesterol, plasmalogens, and sphingolipids. Further analysis of membranes associated with isolated postsynaptic densities (PSDs) suggests the PSD-associated postsynaptic plasma membrane (PSD-PM) as one specific location of synaptic remodeling. We analyze the biophysical consequences of developmental remodeling in reconstituted synaptic membranes and observe remarkably stable microdomains, with the stability of domains increasing with developmental age. We rationalize the developmental accumulation of microdomain-forming lipids in synapses by proposing a mechanism by which palmitoylation of the immobilized scaffold protein PSD-95 nucleates domains at the postsynaptic plasma membrane. These results reveal developmental changes in lipid composition and palmitoylation that facilitate the formation of postsynaptic membrane microdomains, which may serve key roles in the function of the neuronal synapse. © 2016 Tulodziecka et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  6. [Biophysical methods in assessment of the skin microcirculation system].

    Science.gov (United States)

    Dynnik, O B; Mostovoĭ, S E; Berezovskiĭ, V A

    2008-01-01

    In this work has been analyzed the potential of biophysics methods in estimations of the microcirculatory system. Capillaroresistometry, Computer capillaroscopy and Laser Doppler Flowmetry can to detect of the endothelial dysfunction in the patients with chronic hepatic diseases. This instrumentals biophysics methods may be used in clinical investigations for screening early pathological conditions with dysfunction of the microcirculatory system. The methods Laser Doppler Flowmetry is important for investigations the patients with others diseases and for dynamical monitoring by quality of the treatment. The purpose of these methods an objective estimation of disorders in the microcirculatory system.

  7. FIB patterning of dielectric, metallized and graphene membranes: A comparative study

    International Nuclear Information System (INIS)

    Hemamouche, A.; Morin, A.; Bourhis, E.; Madouri, A.; Lafosse, X.; Ulysse, C.; Guilet, S.; Patriarche, G.; Gierak, J.; Toury, B.; Tarnaud, E.; Mathe, J.; Guegan, P.; Auvray, L.; Montel, F.; Wilmart, Q.; Placais, B.; Yates, J.

    2014-01-01

    Fabrication of nano-pores and nano-masks has recently emerged as an area of considerable interest for research applications ranging from optics, to electronics and to biophysics. In this work we evaluate and compare the fabrication of nano-pores, using a finely focused gallium beam, in free-standing membranes/films made of Si, SiN, and SiO 2 (having thicknesses of a few tens of nanometers) and also in graphene and hexagonal boron nitride (h-BN) atomically thin suspended sheets. Mechanical resistance, charging effects and patterning performances are evaluated and compared. In spite of the very different properties of the membranes we report that reproducible nano-pore fabrication in the sub-10 nm range can be achieved in both amorphous and atomically thin sheets using Ga + focused ion beams (FIB). (authors)

  8. Gamma-irradiation and neutron effect on DNA-membrane complexes of mammalian cells

    International Nuclear Information System (INIS)

    Lapidus, I.L.; Nazarov, V.M.; Ehrtsgreber, G.

    1984-01-01

    The first results of radiobiological investigations in the biophysical channel of the JINR reactor IBR-2 are presented. Sedimentation behaviour of DNA-membrane complexes has been studied at irradiation of the Chinese hamster cells (VT9-4) in a wide dose range of 137 Cs γ-irradiation and neutrons. An earlier assumption of the authors on the role of DNA double-strand breaks in changing the relative sedimentation velocity of complexes at irradiation of cells with doses over 50 Gy has been confirmed

  9. Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease

    OpenAIRE

    Hosseini, Poorya; Abidi, Sabia Z.; Du, E; Papageorgiou, Dimitrios P.; Choi, Youngwoon; Park, YongKeun; Higgins, John M.; Kato, Gregory J.; Suresh, Subra; Dao, Ming; Yaqoob, Zahid; So, Peter T. C.

    2016-01-01

    There exists a critical need for developing biomarkers reflecting clinical outcomes and for evaluating the effectiveness of treatments for sickle cell disease patients. Prior attempts to find such patient-specific markers have mostly relied upon chemical biomarkers or biophysical properties at hypoxia with limited success. We introduce unique biomarkers based on characterization of cellular biophysical properties at normoxia and show that these markers correlate sensitively with treatment usi...

  10. Chemical synthesis of membrane proteins by the removable backbone modification method.

    Science.gov (United States)

    Tang, Shan; Zuo, Chao; Huang, Dong-Liang; Cai, Xiao-Ying; Zhang, Long-Hua; Tian, Chang-Lin; Zheng, Ji-Shen; Liu, Lei

    2017-12-01

    Chemical synthesis can produce membrane proteins bearing specifically designed modifications (e.g., phosphorylation, isotope labeling) that are difficult to obtain through recombinant protein expression approaches. The resulting homogeneously modified synthetic membrane proteins are valuable tools for many advanced biochemical and biophysical studies. This protocol describes the chemical synthesis of membrane proteins by condensation of transmembrane peptide segments through native chemical ligation. To avoid common problems encountered due to the poor solubility of transmembrane peptides in almost any solvent, we describe an effective procedure for the chemical synthesis of membrane proteins through the removable-backbone modification (RBM) strategy. Two key steps of this protocol are: (i) installation of solubilizing Arg4-tagged RBM groups into the transmembrane peptides at any primary amino acid through Fmoc (9-fluorenylmethyloxycarbonyl) solid-phase peptide synthesis and (ii) native ligation of the full-length sequence, followed by removal of the RBM tags by TFA (trifluoroacetic acid) cocktails to afford the native protein. The installation of RBM groups is achieved by using 4-methoxy-5-nitrosalicyladehyde by reduction amination to incorporate an activated O-to-N acyl transfer auxiliary. The Arg4-tag-modified membrane-spanning peptide segments behave like water-soluble peptides to facilitate their purification, ligation and mass characterization.

  11. Biophysical behavior of Scomberoides commersonianus skin collagen.

    Science.gov (United States)

    Kolli, Nagamalleswari; Joseph, K Thomas; Ramasami, T

    2002-06-01

    Some biophysical characteristics of the skin collagen from Scomberoides commersonianus were measured and compared to those of rat tail tendon. Stress-strain data indicate that the strain at break as well as the tensile strength of the fish skin without scales increased significantly. The maximum tension in case of rat skin is at least a factor of two higher than that observed in fish skin. The much lower hydrothermal isometric tension measurements observed in fish skin are attributable to a lesser number of heat stable crosslinks. Stress relaxation measurements in the fish skin indicate that more than one relaxation process may be involved in the stabilization of collagenous matrix. The observed differences in the biophysical behavior of fish skin may well arise from combination of changes in extent of hydroxylation of proline in collagen synthesis, hydrogen bond network and fibril orientation as compared to rat tail tendon.

  12. Detecting subtle plasma membrane perturbation in living cells using second harmonic generation imaging.

    Science.gov (United States)

    Moen, Erick K; Ibey, Bennett L; Beier, Hope T

    2014-05-20

    The requirement of center asymmetry for the creation of second harmonic generation (SHG) signals makes it an attractive technique for visualizing changes in interfacial layers such as the plasma membrane of biological cells. In this article, we explore the use of lipophilic SHG probes to detect minute perturbations in the plasma membrane. Three candidate probes, Di-4-ANEPPDHQ (Di-4), FM4-64, and all-trans-retinol, were evaluated for SHG effectiveness in Jurkat cells. Di-4 proved superior with both strong SHG signal and limited bleaching artifacts. To test whether rapid changes in membrane symmetry could be detected using SHG, we exposed cells to nanosecond-pulsed electric fields, which are believed to cause formation of nanopores in the plasma membrane. Upon nanosecond-pulsed electric fields exposure, we observed an instantaneous drop of ~50% in SHG signal from the anodic pole of the cell. When compared to the simultaneously acquired fluorescence signals, it appears that the signal change was not due to the probe diffusing out of the membrane or changes in membrane potential or fluidity. We hypothesize that this loss in SHG signal is due to disruption in the interfacial nature of the membrane. The results show that SHG imaging has great potential as a tool for measuring rapid and subtle plasma membrane disturbance in living cells. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  13. Cell biology, biophysics, and mechanobiology: From the basics to Clinics.

    Science.gov (United States)

    Zeng, Y

    2017-04-29

    Cell biology, biomechanics and biophysics are the key subjects that guide our understanding in diverse areas of tissue growth, development, remodeling and homeostasis. Novel discoveries such as molecular mechanism, and mechanobiological mechanism in cell biology, biomechanics and biophysics play essential roles in our understanding of the pathogenesis of various human diseases, as well as in designing the treatment of these diseases. In addition, studies in these areas will also facilitate early diagnostics of human diseases, such as cardiovascular diseases and cancer. In this special issue, we collected 10 original research articles and 1 review...

  14. Temperature and cholera toxin B are factors that influence formation of membrane nanotubes in RT4 and T24 urothelial cancer cell lines

    Directory of Open Access Journals (Sweden)

    Doron Kabaso

    2011-03-01

    Full Text Available Doron Kabaso1*, Maruša Lokar1*, Veronika Kralj-Iglic2, Peter Veranic3, Aleš Iglic11Laboratory of Biophysics, Faculty of Electrical Engineering, 2Laboratory of Clinical Biophysics, Faculty of Medicine, 3Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; *These two authors equally share the first authorshipAbstract: The growth of membrane nanotubes is crucial for intercellular communication in both normal development and pathological conditions. Therefore, identifying factors that influence their stability and formation are important for both basic research and in development of potential treatments of pathological states. Here we investigate the effect of cholera toxin B (CTB and temperature on two pathological model systems: urothelial cell line RT4, as a model system of a benign tumor, and urothelial cell line T24, as a model system of a metastatic tumor. In particular, the number of intercellular membrane nanotubes (ICNs; ie, membrane nanotubes that bridge neighboring cells was counted. In comparison with RT4 cells, we reveal a significantly higher number in the density of ICNs in T24 cells not derived from RT4 without treatments (P = 0.005, after 20 minutes at room temperature (P = 0.0007, and following CTB treatment (P = 0.000025. The binding of CTB to GM1–lipid complexes in membrane exvaginations or tips of membrane nanotubes may reduce the positive spontaneous (intrinsic curvature of GM1–lipid complexes, which may lead to lipid mediated attractive interactions between CTB–GM1–lipid complexes, their aggregation and consequent formation of enlarged spherical tips of nanotubes. The binding of CTB to GM1 molecules in the outer membrane leaflet of membrane exvaginations and tips of membrane nanotubes may also increase the area difference between the two leaflets and in this way facilitate the growth of membrane nanotubes.Keywords: cancer cells, membrane nanotubes, cholera toxin

  15. A PtdIns(4)P-driven electrostatic field controls cell membrane identity and signalling in plants.

    Science.gov (United States)

    Simon, Mathilde Laetitia Audrey; Platre, Matthieu Pierre; Marquès-Bueno, Maria Mar; Armengot, Laia; Stanislas, Thomas; Bayle, Vincent; Caillaud, Marie-Cécile; Jaillais, Yvon

    2016-06-20

    Many signalling proteins permanently or transiently localize to specific organelles. It is well established that certain lipids act as biochemical landmarks to specify compartment identity. However, they also influence membrane biophysical properties, which emerge as important features in specifying cellular territories. Such parameters include the membrane inner surface potential, which varies according to the lipid composition of each organelle. Here, we found that the plant plasma membrane (PM) and the cell plate of dividing cells have a unique electrostatic signature controlled by phosphatidylinositol-4-phosphate (PtdIns(4)P). Our results further reveal that, contrarily to other eukaryotes, PtdIns(4)P massively accumulates at the PM, establishing it as a critical hallmark of this membrane in plants. Membrane surface charges control the PM localization and function of the polar auxin transport regulator PINOID as well as proteins from the BRI1 KINASE INHIBITOR1 (BKI1)/MEMBRANE ASSOCIATED KINASE REGULATOR (MAKR) family, which are involved in brassinosteroid and receptor-like kinase signalling. We anticipate that this PtdIns(4)P-driven physical membrane property will control the localization and function of many proteins involved in development, reproduction, immunity and nutrition.

  16. Sonographic biophysical profile in detection of foetal hypoxia in 100 cases of suspected high risk pregnancy

    International Nuclear Information System (INIS)

    Ullah, N.; Khan, A.R.; Usman, M.

    2010-01-01

    Background: The foetus has become increasingly accessible and visible as a patient over the last two decades. Ultrasound imaging has broadened the scope of foetal assessment. Dynamic real time B-Mode ultrasound is used to monitor cluster of biophysical variables, both dynamic and static collectively termed as biophysical profile. The purpose of this study was to determine the effect of sonographic biophysical profile score on perinatal outcome in terms of mortality and morbidity. Methods: This descriptive study was carried on 100 randomly select ed high risk pregnant patients in Radiology Department PGMI, Government Lady Reading Hospital, Peshawar from December 2007 to June 2008. Manning biophysical profile including non-stress was employed for foetal screening, using Toshiba ultrasound machine model Nemio SSA-550A and 7.5 MHZ probe. Results: Out of 100 cases 79 (79%) had a normal biophysical profile in the last scan of 10/10 and had a normal perinatal outcome with 5 minutes Apgar score >7/10. In 13 (13%) cases Apgar score at 5 minute was < 7/10 and babies were shifted to nursery. There were 2 (2%) false positive cases that showed abnormal biophysical profile scores of 6/10 but babies were born with an Apgar score of 8/10 at 5 minutes. There were 2 (2%) neonatal deaths in this study group. The sensitivity of biophysical profile was 79.1%, specificity 92.9%. Predictive value for a positive test was 98.55%; predictive value for a negative test was 41.93%. Conclusion: Biophysical profile is highly accurate and reliable test of diagnosing foetal hypoxia. (author)

  17. Effect of ambient light on the time needed to complete a fetal biophysical profile: A randomized controlled trial.

    Science.gov (United States)

    Said, Heather M; Gupta, Shweta; Vricella, Laura K; Wand, Katy; Nguyen, Thinh; Gross, Gilad

    2017-10-01

    The objective of this study is to determine whether ambient light serves as a fetal stimulus to decrease the amount of time needed to complete a biophysical profile. This is a randomized controlled trial of singleton gestations undergoing a biophysical profile. Patients were randomized to either ambient light or a darkened room. The primary outcome was the time needed to complete the biophysical profile. Secondary outcomes included total and individual component biophysical profile scores and scores less than 8. A subgroup analysis of different maternal body mass indices was also performed. 357 biophysical profile studies were analyzed. 182 studies were performed with ambient light and 175 were performed in a darkened room. There was no difference in the median time needed to complete the biophysical profile based on exposure to ambient light (6.1min in darkened room versus 6.6min with ambient light; P=0.73). No difference was found in total or individual component biophysical profile scores. Subgroup analysis by maternal body mass index did not demonstrate shorter study times with ambient light exposure in women who were normal weight, overweight or obese. Ambient light exposure did not decrease the time needed to complete the biophysical profile. There was no evidence that ambient light altered fetal behavior observed during the biophysical profile. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Synthetic Biology: Engineering Living Systems from Biophysical Principles.

    Science.gov (United States)

    Bartley, Bryan A; Kim, Kyung; Medley, J Kyle; Sauro, Herbert M

    2017-03-28

    Synthetic biology was founded as a biophysical discipline that sought explanations for the origins of life from chemical and physical first principles. Modern synthetic biology has been reinvented as an engineering discipline to design new organisms as well as to better understand fundamental biological mechanisms. However, success is still largely limited to the laboratory and transformative applications of synthetic biology are still in their infancy. Here, we review six principles of living systems and how they compare and contrast with engineered systems. We cite specific examples from the synthetic biology literature that illustrate these principles and speculate on their implications for further study. To fully realize the promise of synthetic biology, we must be aware of life's unique properties. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  19. Biophysics and the Challenges of Emerging Threats

    CERN Document Server

    Puglisi, Joseph D

    2009-01-01

    This volume is a collection of articles from the proceedings of the International School of Structural Biology and Magnetic Resonance 8th Course: Biophysics and the Challenges of Emerging Threats. This NATO Advance Study Institute (ASI) was held in Erice at the Ettore Majorana Foundation and Centre for Scientific Culture on 19 through 30 June 2007. The ASI brought together a diverse group of experts who bridged the fields of virology and biology, biophysics, chemistry and physics. Prominent lecturers and students from around the world representant a total of 24 countries participated in the NATO ASI organized by Professors Joseph Puglisi (Stanford University, USA) and Alexander Arseniev (Moscow, RU). The central hypothesis underlying this ASI was that interdisciplinary research, merging principles of physics, chemistry and biology, can drive new discovery in detecting and fighting bioterrorism agents, lead to cleaner environments, and help propel development in NATO partner countries. The ASI merged the relat...

  20. Festschrift in the honor of Stephen H. White's 70th Birthday.

    Science.gov (United States)

    Bondar, Ana-Nicoleta; Woolf, Thomas B; Tobias, Douglas J

    2011-01-01

    The Symposium 'Frontiers in membrane and membrane protein biophysics: experiments and theory', held this year at the University of California, Irvine (August 19-20), celebrated the 70th Birthday of Stephen H. White by bringing together distinguished experimentalists and theoreticians to discuss the state of the art and future challenges in the field of membrane and membrane protein biophysics. The meeting and this special issue highlight the highly interdisciplinary nature of membrane and membrane protein biophysics, and the tremendous contributions that S. H. White and his lab have brought to the field.

  1. Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease.

    Science.gov (United States)

    Hosseini, Poorya; Abidi, Sabia Z; Du, E; Papageorgiou, Dimitrios P; Choi, Youngwoon; Park, YongKeun; Higgins, John M; Kato, Gregory J; Suresh, Subra; Dao, Ming; Yaqoob, Zahid; So, Peter T C

    2016-08-23

    Hydroxyurea (HU) has been used clinically to reduce the frequency of painful crisis and the need for blood transfusion in sickle cell disease (SCD) patients. However, the mechanisms underlying such beneficial effects of HU treatment are still not fully understood. Studies have indicated a weak correlation between clinical outcome and molecular markers, and the scientific quest to develop companion biophysical markers have mostly targeted studies of blood properties under hypoxia. Using a common-path interferometric technique, we measure biomechanical and morphological properties of individual red blood cells in SCD patients as a function of cell density, and investigate the correlation of these biophysical properties with drug intake as well as other clinically measured parameters. Our results show that patient-specific HU effects on the cellular biophysical properties are detectable at normoxia, and that these properties are strongly correlated with the clinically measured mean cellular volume rather than fetal hemoglobin level.

  2. Sphingolipid Organization in the Plasma Membrane and the Mechanisms That Influence It.

    Science.gov (United States)

    Kraft, Mary L

    2016-01-01

    Sphingolipids are structural components in the plasma membranes of eukaryotic cells. Their metabolism produces bioactive signaling molecules that modulate fundamental cellular processes. The segregation of sphingolipids into distinct membrane domains is likely essential for cellular function. This review presents the early studies of sphingolipid distribution in the plasma membranes of mammalian cells that shaped the most popular current model of plasma membrane organization. The results of traditional imaging studies of sphingolipid distribution in stimulated and resting cells are described. These data are compared with recent results obtained with advanced imaging techniques, including super-resolution fluorescence detection and high-resolution secondary ion mass spectrometry (SIMS). Emphasis is placed on the new insight into the sphingolipid organization within the plasma membrane that has resulted from the direct imaging of stable isotope-labeled lipids in actual cell membranes with high-resolution SIMS. Super-resolution fluorescence techniques have recently revealed the biophysical behaviors of sphingolipids and the unhindered diffusion of cholesterol analogs in the membranes of living cells are ultimately in contrast to the prevailing hypothetical model of plasma membrane organization. High-resolution SIMS studies also conflicted with the prevailing hypothesis, showing sphingolipids are concentrated in micrometer-scale membrane domains, but cholesterol is evenly distributed within the plasma membrane. Reductions in cellular cholesterol decreased the number of sphingolipid domains in the plasma membrane, whereas disruption of the cytoskeleton eliminated them. In addition, hemagglutinin, a transmembrane protein that is thought to be a putative raft marker, did not cluster within sphingolipid-enriched regions in the plasma membrane. Thus, sphingolipid distribution in the plasma membrane is dependent on the cytoskeleton, but not on favorable interactions with

  3. Biophysical radiosensitization

    International Nuclear Information System (INIS)

    Vladescu, C.; Apetroae, M.

    1983-01-01

    Experimental studies on normal and tumor-bearing rats revealed that chronic treatment with hydroquinone (5 mg/kg/day) inhibited catalase activity in liver, spleen, blood, and H 18R tumor. 3 H-hydroquinone (1.5 μCi/g body weight) showed tumor specificity, with maximum radioactivity in the tumor at 1 h after administration. The biological half-time of 3 H-hydroquinone in the tumor was 2 h, but there seems to exist a longer component, since 24 h after administration, some 30% of the maximum radioactivity could be detected in the tumor. Hydroquinone treatment produces a specific inhibition of catalase in the tumor and a higher degree of oxygenation at this level. These findings support the assumption that the mechanism of action of hydroquinone as an anticancer agent is achieved mainly via peroxide production. The oxygenation of the hypoxic tumoral tissue is done at non-toxic levels of hydroquinone, through a natural and specific biophysical pathway, recommanding hydroquinone for combined anticancer treatment (radiotherapy and chemotherapy). (orig.)

  4. RESEARCH ON REDUCING PREMATURITY RUPTURE OF MEMBRANE

    Directory of Open Access Journals (Sweden)

    Maria URSACHI (BOLOTA

    2016-12-01

    -term (3 days and distance (2 years interventional methods applied; clinical investigation of complications arising post intervention; studying behavior synthetic amnion. Conclusions: The cause of PRAS is multifactorial. Traditionally, fetal membrane rupture has been attributed to increased physical stress, which weakens the membranes. At the molecular level PRAS is the result of reducing collagen synthesis, alteration of the structure of collagen to accelerate degradation. In addition, these biochemical changes can be amplified and biophysical stress today. The priorities of this research include elucidation of the normal biological process of fetal membranes, including extracellular matrix remodeling, apoptosis.

  5. The biophysics of renal sympathetic denervation using radiofrequency energy.

    Science.gov (United States)

    Patel, Hitesh C; Dhillon, Paramdeep S; Mahfoud, Felix; Lindsay, Alistair C; Hayward, Carl; Ernst, Sabine; Lyon, Alexander R; Rosen, Stuart D; di Mario, Carlo

    2014-05-01

    Renal sympathetic denervation is currently performed in the treatment of resistant hypertension by interventionists who otherwise do not typically use radiofrequency (RF) energy ablation in their clinical practice. Adequate RF lesion formation is dependent upon good electrode-tissue contact, power delivery, electrode-tissue interface temperature, target-tissue impedance and the size of the catheter's active electrode. There is significant interplay between these variables and hence an appreciation of the biophysical determinants of RF lesion formation is required to provide effective and safe clinical care to our patients. In this review article, we summarize the biophysics of RF ablation and explain why and how complications of renal sympathetic denervation may occur and discuss methods to minimise them.

  6. The biophysical link between climate, water, and vegetation in bioenergy agro-ecosystems

    International Nuclear Information System (INIS)

    Bagley, Justin E.; Davis, Sarah C.; Georgescu, Matei; Hussain, Mir Zaman; Miller, Jesse; Nesbitt, Stephen W.; VanLoocke, Andy; Bernacchi, Carl J.

    2014-01-01

    Land use change for bioenergy feedstocks is likely to intensify as energy demand rises simultaneously with increased pressure to minimize greenhouse gas emissions. Initial assessments of the impact of adopting bioenergy crops as a significant energy source have largely focused on the potential for bioenergy agroecosystems to provide global-scale climate regulating ecosystem services via biogeochemical processes. Such as those processes associated with carbon uptake, conversion, and storage that have the potential to reduce global greenhouse gas emissions (GHG). However, the expansion of bioenergy crops can also lead to direct biophysical impacts on climate through water regulating services. Perturbations of processes influencing terrestrial energy fluxes can result in impacts on climate and water across a spectrum of spatial and temporal scales. Here, we review the current state of knowledge about biophysical feedbacks between vegetation, water, and climate that would be affected by bioenergy-related land use change. The physical mechanisms involved in biophysical feedbacks are detailed, and interactions at leaf, field, regional, and global spatial scales are described. Locally, impacts on climate of biophysical changes associated with land use change for bioenergy crops can meet or exceed the biogeochemical changes in climate associated with rising GHG's, but these impacts have received far less attention. Realization of the importance of ecosystems in providing services that extend beyond biogeochemical GHG regulation and harvestable yields has led to significant debate regarding the viability of various feedstocks in many locations. The lack of data, and in some cases gaps in knowledge associated with biophysical and biochemical influences on land–atmosphere interactions, can lead to premature policy decisions. - Highlights: • The physical basis for biophysical impacts of expanding bioenergy agroecosystems on climate and water is described. • We

  7. Raman spectroscopy reveals biophysical markers in skin cancer surgical margins

    Science.gov (United States)

    Feng, Xu; Moy, Austin J.; Nguyen, Hieu T. M.; Zhang, Yao; Fox, Matthew C.; Sebastian, Katherine R.; Reichenberg, Jason S.; Markey, Mia K.; Tunnell, James W.

    2018-02-01

    The recurrence rate of nonmelanoma skin cancer is highly related to the residual tumor after surgery. Although tissueconserving surgery, such as Mohs surgery, is a standard method for the treatment of nonmelanoma skin cancer, they are limited by lengthy and costly frozen-section histopathology. Raman spectroscopy (RS) is proving to be an objective, sensitive, and non-destructive tool for detecting skin cancer. Previous studies demonstrated the high sensitivity of RS in detecting tumor margins of basal cell carcinoma (BCC). However, those studies rely on statistical classification models and do not elucidate the skin biophysical composition. As a result, we aim to discover the biophysical differences between BCC and primary normal skin structures (including epidermis, dermis, hair follicle, sebaceous gland and fat). We obtained freshly resected ex vivo skin samples from fresh resection specimens from 14 patients undergoing Mohs surgery. Raman images were acquired from regions containing one or more structures using a custom built 830nm confocal Raman microscope. The spectra were grouped using K-means clustering analysis and annotated as either BCC or each of the five normal structures by comparing with the histopathology image of the serial section. The spectral data were then fit by a previously established biophysical model with eight primary skin constituents. Our results show that BCC has significant differences in the fit coefficients of nucleus, collagen, triolein, keratin and elastin compared with normal structures. Our study reveals RS has the potential to detect biophysical changes in resection margins, and supports the development of diagnostic algorithms for future intraoperative implementation of RS during Mohs surgery.

  8. Non-Brownian diffusion in lipid membranes: Experiments and simulations.

    Science.gov (United States)

    Metzler, R; Jeon, J-H; Cherstvy, A G

    2016-10-01

    The dynamics of constituents and the surface response of cellular membranes-also in connection to the binding of various particles and macromolecules to the membrane-are still a matter of controversy in the membrane biophysics community, particularly with respect to crowded membranes of living biological cells. We here put into perspective recent single particle tracking experiments in the plasma membranes of living cells and supercomputing studies of lipid bilayer model membranes with and without protein crowding. Special emphasis is put on the observation of anomalous, non-Brownian diffusion of both lipid molecules and proteins embedded in the lipid bilayer. While single component, pure lipid bilayers in simulations exhibit only transient anomalous diffusion of lipid molecules on nanosecond time scales, the persistence of anomalous diffusion becomes significantly longer ranged on the addition of disorder-through the addition of cholesterol or proteins-and on passing of the membrane lipids to the gel phase. Concurrently, experiments demonstrate the anomalous diffusion of membrane embedded proteins up to macroscopic time scales in the minute time range. Particular emphasis will be put on the physical character of the anomalous diffusion, in particular, the occurrence of ageing observed in the experiments-the effective diffusivity of the measured particles is a decreasing function of time. Moreover, we present results for the time dependent local scaling exponent of the mean squared displacement of the monitored particles. Recent results finding deviations from the commonly assumed Gaussian diffusion patterns in protein crowded membranes are reported. The properties of the displacement autocorrelation function of the lipid molecules are discussed in the light of their appropriate physical anomalous diffusion models, both for non-crowded and crowded membranes. In the last part of this review we address the upcoming field of membrane distortion by elongated membrane

  9. Manipulating lipid membrane architecture by liquid crystal-analog curvature elasticity (Presentation Recording)

    Science.gov (United States)

    Lee, Sin-Doo

    2015-10-01

    Soft matters such as liquid crystals and biological molecules exhibit a variety of interesting physical phenomena as well as new applications. Recently, in mimicking biological systems that have the ability to sense, regulate, grow, react, and regenerate in a highly responsive and self-adaptive manner, the significance of the liquid crystal order in living organisms, for example, a biological membrane possessing the lamellar order, is widely recognized from the viewpoints of physics and chemistry of interfaces and membrane biophysics. Lipid bilayers, resembling cell membranes, provide primary functions for the transport of biological components of ions and molecules in various cellular activities, including vesicle budding and membrane fusion, through lateral organization of the membrane components such as proteins. In this lecture, I will describe how the liquid crystal-analog curvature elasticity of a lipid bilayer plays a critical role in developing a new platform for understanding diverse biological functions at a cellular level. The key concept is to manipulate the local curvature at an interface between a solid substrate and a model membrane. Two representative examples will be demonstrated: one of them is the topographic control of lipid rafts in a combinatorial array where the ligand-receptor binding event occurs and the other concerns the reconstitution of a ring-type lipid raft in bud-mimicking architecture within the framework of the curvature elasticity.

  10. X-Ray structure and biophysical properties of rabbit fibroblast growth factor 1

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jihun; Blaber, Sachiko I.; Irsigler, Andre; Aspinwall, Eric; Blaber, Michael; (FSU)

    2010-01-14

    The rabbit is an important and de facto animal model in the study of ischemic disease and angiogenic therapy. Additionally, fibroblast growth factor 1 (FGF-1) is emerging as one of the most important growth factors for novel pro-angiogenic and pro-arteriogenic therapy. However, despite its significance, the fundamental biophysical properties of rabbit FGF-1, including its X-ray structure, have never been reported. Here, the cloning, crystallization, X-ray structure and determination of the biophysical properties of rabbit FGF-1 are described. The X-ray structure shows that the amino-acid differences between human and rabbit FGF-1 are solvent-exposed and therefore potentially immunogenic, while the biophysical studies identify differences in thermostability and receptor-binding affinity that distinguish rabbit FGF-1 from human FGF-1.

  11. A New Strain Collection for Improved Expression of Outer Membrane Proteins

    Directory of Open Access Journals (Sweden)

    Ina Meuskens

    2017-11-01

    Full Text Available Almost all integral membrane proteins found in the outer membranes of Gram-negative bacteria belong to the transmembrane β-barrel family. These proteins are not only important for nutrient uptake and homeostasis, but are also involved in such processes as adhesion, protein secretion, biofilm formation, and virulence. As surface exposed molecules, outer membrane β-barrel proteins are also potential drug and vaccine targets. High production levels of heterologously expressed proteins are desirable for biochemical and especially structural studies, but over-expression and subsequent purification of membrane proteins, including outer membrane proteins, can be challenging. Here, we present a set of deletion mutants derived from E. coli BL21(DE3 designed for the over-expression of recombinant outer membrane proteins. These strains harbor deletions of four genes encoding abundant β-barrel proteins in the outer membrane (OmpA, OmpC, OmpF, and LamB, both single and in all combinations of double, triple, and quadruple knock-outs. The sequences encoding these outer membrane proteins were deleted completely, leaving only a minimal scar sequence, thus preventing the possibility of genetic reversion. Expression tests in the quadruple mutant strain with four test proteins, including a small outer membrane β-barrel protein and variants thereof as well as two virulence-related autotransporters, showed significantly improved expression and better quality of the produced proteins over the parent strain. Differences in growth behavior and aggregation in the presence of high salt were observed, but these phenomena did not negatively influence the expression in the quadruple mutant strain when handled as we recommend. The strains produced in this study can be used for outer membrane protein production and purification, but are also uniquely useful for labeling experiments for biophysical measurements in the native membrane environment.

  12. Structure of anti-FLAG M2 Fab domain and its use in the stabilization of engineered membrane proteins

    International Nuclear Information System (INIS)

    Roosild, Tarmo P.; Castronovo, Samantha; Choe, Senyon

    2006-01-01

    The X-ray crystallographic analysis of anti-FLAG M2 Fab is reported and the implications of the structure on FLAG epitope binding are described as a first step in the development of a tool for the structural and biophysical study of membrane proteins. The inherent difficulties of stabilizing detergent-solubilized integral membrane proteins for biophysical or structural analysis demand the development of new methodologies to improve success rates. One proven strategy is the use of antibody fragments to increase the ‘soluble’ portion of any membrane protein, but this approach is limited by the difficulties and expense associated with producing monoclonal antibodies to an appropriate exposed epitope on the target protein. Here, the stabilization of a detergent-solubilized K + channel protein, KvPae, by engineering a FLAG-binding epitope into a known loop region of the protein and creating a complex with Fab fragments from commercially available anti-FLAG M2 monoclonal antibodies is reported. Although well diffracting crystals of the complex have not yet been obtained, during the course of crystallization trials the structure of the anti-FLAG M2 Fab domain was solved to 1.86 Å resolution. This structure, which should aid future structure-determination efforts using this approach by facilitating molecular-replacement phasing, reveals that the binding pocket appears to be specific only for the first four amino acids of the traditional FLAG epitope, namely DYKD. Thus, the use of antibody fragments for improving the stability of target proteins can be rapidly applied to the study of membrane-protein structure by placing the short DKYD motif within a predicted peripheral loop of that protein and utilizing commercially available anti-FLAG M2 antibody fragments

  13. Chief, Structural Biophysics Laboratory | Center for Cancer Research

    Science.gov (United States)

    The SBL Chief is expected to establish a strong research program in structural biology/biophysics in addition to providing leadership of the SBL and the structural biology community in the NCI Intramural Program.  Applicants should hold a Ph.D., M.D./Ph.D., or equivalent doctoral degree in a relevant discipline, and should possess outstanding communication skills and documented leadership experience.  Tenured faculty or industrial scientists of equivalent rank with a demonstrated commitment to structural biophysics should apply.  Salary will be commensurate with experience and accomplishments.  This position is not restricted to U.S. citizens. A full civil service package of benefits (including health insurance, life insurance, and retirement) is available. This position is subject to a background investigation.  The NIH is dedicated to building a diverse community in its training and employment programs.

  14. Satellite mapping of surface biophysical parameters at the biome scale over the North American grasslands: A case study

    Science.gov (United States)

    Wylie, B.K.; Meyer, D.J.; Tieszen, L.L.; Mannel, S.

    2002-01-01

    Quantification of biophysical parameters is needed by terrestrial process modeling and other applications. A study testing the role of multispectral data for monitoring biophysical parameters was conducted over a network of grassland field sites in the Great Plains of North America. Grassland biophysical parameters [leaf area index (LAI), fraction of absorbed photosynthetically active radiation (fPAR), and biomass] and their relationships with ground radiometer normalized difference vegetation index (NDVI) were established in this study (r2=.66–.85) from data collected across the central and northern Great Plains in 1995. These spectral/biophysical relationships were compared to 1996 field data from the Tallgrass Prairie Preserve in northeastern Oklahoma and showed no consistent biases, with most regression estimates falling within the respective 95% confidence intervals. Biophysical parameters were estimated for 21 “ground pixels” (grids) at the Tallgrass Prairie Preserve in 1996, representing three grazing/burning treatments. Each grid was 30×30 m in size and was systematically sampled with ground radiometer readings. The radiometric measurements were then converted to biophysical parameters and spatially interpolated using geostatistical kriging. Grid-based biophysical parameters were monitored through the growing season and regressed against Landsat Thematic Mapper (TM) NDVI (r2=.92–.94). These regression equations were used to estimate biophysical parameters for grassland TM pixels over the Tallgrass Prairie Preserve in 1996. This method maintained consistent regression development and prediction scales and attempted to minimize scaling problems associated with mixed land cover pixels. A method for scaling Landsat biophysical parameters to coarser resolution satellite data sets (1 km2) was also investigated.

  15. Membrane-Wrapping Contributions to Malaria Parasite Invasion of the Human Erythrocyte

    Science.gov (United States)

    Dasgupta, Sabyasachi; Auth, Thorsten; Gov, Nir S.; Satchwell, Timothy J.; Hanssen, Eric; Zuccala, Elizabeth S.; Riglar, David T.; Toye, Ashley M.; Betz, Timo; Baum, Jake; Gompper, Gerhard

    2014-01-01

    The blood stage malaria parasite, the merozoite, has a small window of opportunity during which it must successfully target and invade a human erythrocyte. The process of invasion is nonetheless remarkably rapid. To date, mechanistic models of invasion have focused predominantly on the parasite actomyosin motor contribution to the energetics of entry. Here, we have conducted a numerical analysis using dimensions for an archetypal merozoite to predict the respective contributions of the host-parasite interactions to invasion, in particular the role of membrane wrapping. Our theoretical modeling demonstrates that erythrocyte membrane wrapping alone, as a function of merozoite adhesive and shape properties, is sufficient to entirely account for the first key step of the invasion process, that of merozoite reorientation to its apex and tight adhesive linkage between the two cells. Next, parasite-induced reorganization of the erythrocyte cytoskeleton and release of parasite-derived membrane can also account for a considerable energetic portion of actual invasion itself, through membrane wrapping. Thus, contrary to the prevailing dogma, wrapping by the erythrocyte combined with parasite-derived membrane release can markedly reduce the expected contributions of the merozoite actomyosin motor to invasion. We therefore propose that invasion is a balance between parasite and host cell contributions, evolved toward maximal efficient use of biophysical forces between the two cells. PMID:24988340

  16. Developing spatial biophysical accounting for multiple ecosystem services

    NARCIS (Netherlands)

    Remme, R.P.; Schroter, M.; Hein, L.G.

    2014-01-01

    Ecosystem accounting is receiving increasing interest as a way to systematically monitor the conditions of ecosystems and the ecosystem services they provide. A critical element of ecosystem accounting is understanding spatially explicit flows of ecosystem services. We developed spatial biophysical

  17. Achievements and challenges in structural bioinformatics and computational biophysics.

    Science.gov (United States)

    Samish, Ilan; Bourne, Philip E; Najmanovich, Rafael J

    2015-01-01

    The field of structural bioinformatics and computational biophysics has undergone a revolution in the last 10 years. Developments that are captured annually through the 3DSIG meeting, upon which this article reflects. An increase in the accessible data, computational resources and methodology has resulted in an increase in the size and resolution of studied systems and the complexity of the questions amenable to research. Concomitantly, the parameterization and efficiency of the methods have markedly improved along with their cross-validation with other computational and experimental results. The field exhibits an ever-increasing integration with biochemistry, biophysics and other disciplines. In this article, we discuss recent achievements along with current challenges within the field. © The Author 2014. Published by Oxford University Press.

  18. Evolution and Biophysics of the Escherichia coli lac Operon

    Science.gov (United States)

    Ray, J. Christian; Igoshin, Oleg; Quan, Selwyn; Monds, Russell; Cooper, Tim; Balázsi, Gábor

    2011-03-01

    To understand, predict, and control the evolution of living organisms, we consider biophysical effects and molecular network architectures. The lactose utilization system of E. coli is among the most well-studied molecular networks in biology, making it an ideal candidate for such studies. Simulations show how the genetic architecture of the wild-type operon attenuates large metabolic intermediate fluctuations that are predicted to occur in an equivalent system with the component genes on separate operons. Quantification of gene expression in the lac operon evolved in growth conditions containing constant lactose, alternating with glucose, or constant glucose, shows characteristic gene expression patterns depending on conditions. We are simulating these conditions to show context-dependent biophysical sources and costs of different lac operon architectures.

  19. Direct Scaling of Leaf-Resolving Biophysical Models from Leaves to Canopies

    Science.gov (United States)

    Bailey, B.; Mahaffee, W.; Hernandez Ochoa, M.

    2017-12-01

    Recent advances in the development of biophysical models and high-performance computing have enabled rapid increases in the level of detail that can be represented by simulations of plant systems. However, increasingly detailed models typically require increasingly detailed inputs, which can be a challenge to accurately specify. In this work, we explore the use of terrestrial LiDAR scanning data to accurately specify geometric inputs for high-resolution biophysical models that enables direct up-scaling of leaf-level biophysical processes. Terrestrial LiDAR scans generate "clouds" of millions of points that map out the geometric structure of the area of interest. However, points alone are often not particularly useful in generating geometric model inputs, as additional data processing techniques are required to provide necessary information regarding vegetation structure. A new method was developed that directly reconstructs as many leaves as possible that are in view of the LiDAR instrument, and uses a statistical backfilling technique to ensure that the overall leaf area and orientation distribution matches that of the actual vegetation being measured. This detailed structural data is used to provide inputs for leaf-resolving models of radiation, microclimate, evapotranspiration, and photosynthesis. Model complexity is afforded by utilizing graphics processing units (GPUs), which allows for simulations that resolve scales ranging from leaves to canopies. The model system was used to explore how heterogeneity in canopy architecture at various scales affects scaling of biophysical processes from leaves to canopies.

  20. Single cell wound generates electric current circuit and cell membrane potential variations that requires calcium influx.

    Science.gov (United States)

    Luxardi, Guillaume; Reid, Brian; Maillard, Pauline; Zhao, Min

    2014-07-24

    Breaching of the cell membrane is one of the earliest and most common causes of cell injury, tissue damage, and disease. If the compromise in cell membrane is not repaired quickly, irreversible cell damage, cell death and defective organ functions will result. It is therefore fundamentally important to efficiently repair damage to the cell membrane. While the molecular aspects of single cell wound healing are starting to be deciphered, its bio-physical counterpart has been poorly investigated. Using Xenopus laevis oocytes as a model for single cell wound healing, we describe the temporal and spatial dynamics of the wound electric current circuitry and the temporal dynamics of cell membrane potential variation. In addition, we show the role of calcium influx in controlling electric current circuitry and cell membrane potential variations. (i) Upon wounding a single cell: an inward electric current appears at the wound center while an outward electric current is observed at its sides, illustrating the wound electric current circuitry; the cell membrane is depolarized; calcium flows into the cell. (ii) During cell membrane re-sealing: the wound center current density is maintained for a few minutes before decreasing; the cell membrane gradually re-polarizes; calcium flow into the cell drops. (iii) In conclusion, calcium influx is required for the formation and maintenance of the wound electric current circuitry, for cell membrane re-polarization and for wound healing.

  1. Cholesterol Promotes Protein Binding by Affecting Membrane Electrostatics and Solvation Properties.

    Science.gov (United States)

    Doktorova, Milka; Heberle, Frederick A; Kingston, Richard L; Khelashvili, George; Cuendet, Michel A; Wen, Yi; Katsaras, John; Feigenson, Gerald W; Vogt, Volker M; Dick, Robert A

    2017-11-07

    Binding of the retroviral structural protein Gag to the cellular plasma membrane is mediated by the protein's matrix (MA) domain. Prominent among MA-PM interactions is electrostatic attraction between the positively charged MA domain and the negatively charged plasma membrane inner leaflet. Previously, we reported that membrane association of HIV-1 Gag, as well as purified Rous sarcoma virus (RSV) MA and Gag, depends strongly on the presence of acidic lipids and is enhanced by cholesterol (Chol). The mechanism underlying this enhancement was unclear. Here, using a broad set of in vitro and in silico techniques we addressed molecular mechanisms of association between RSV MA and model membranes, and investigated how Chol enhances this association. In neutron scattering experiments with liposomes in the presence or absence of Chol, MA preferentially interacted with preexisting POPS-rich clusters formed by nonideal lipid mixing, binding peripherally to the lipid headgroups with minimal perturbation to the bilayer structure. Molecular dynamics simulations showed a stronger MA-bilayer interaction in the presence of Chol, and a large Chol-driven increase in lipid packing and membrane surface charge density. Although in vitro MA-liposome association is influenced by disparate variables, including ionic strength and concentrations of Chol and charged lipids, continuum electrostatic theory revealed an underlying dependence on membrane surface potential. Together, these results conclusively show that Chol affects RSV MA-membrane association by making the electrostatic potential at the membrane surface more negative, while decreasing the penalty for lipid headgroup desolvation. The presented approach can be applied to other viral and nonviral proteins. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  2. Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment.

    Science.gov (United States)

    Xiao, Yun; Ahadian, Samad; Radisic, Milica

    2017-02-01

    Progress in biomaterial science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and controlling the cellular microenvironment of the wound tissue are important to improve the wound healing process. In this study, we review different biochemical (e.g., growth factors, peptides, DNA, and RNA) and biophysical (e.g., topographical guidance, pressure, electrical stimulation, and pulsed electromagnetic field) cues providing a functional and instructive acellular matrix to heal diabetic chronic wounds. The biochemical and biophysical signals generally regulate cell-matrix interactions and cell behavior and function inducing the tissue regeneration for chronic wounds. Some technologies and devices have already been developed and used in the clinic employing biochemical and biophysical cues for wound healing applications. These technologies can be integrated with smart biomaterials to deliver therapeutic agents to the wound tissue in a precise and controllable manner. This review provides useful guidance in understanding molecular mechanisms and signals in the healing of diabetic chronic wounds and in designing instructive biomaterials to treat them.

  3. Biophysical models of radiobiological effects

    International Nuclear Information System (INIS)

    Obaturov, G.M.

    1987-01-01

    Radiobiological effect models at different organization levels, developed by the author, are presented. Classification and analysis of concepts and biophysical models at molecular, genetic and cellular levels, developed by Soviet and foreign authors in comparison to inherent models, are conducted from the viewpoint of system approach to radiobiological processes and of modelling principles. Models are compared with each other, limits of their applicability and drawbacks are determined. Evaluation of the model truthfulness is conducted according to a number of criteria, ways of further investigations and experimental examination of some models are proposed

  4. Biophysics of DNA

    CERN Document Server

    Vologodskii, Alexander

    2015-01-01

    Surveying the last sixty years of research, this book describes the physical properties of DNA in the context of its biological functioning. It is designed to enable both students and researchers of molecular biology, biochemistry and physics to better understand the biophysics of DNA, addressing key questions and facilitating further research. The chapters integrate theoretical and experimental approaches, emphasising throughout the importance of a quantitative knowledge of physical properties in building and analysing models of DNA functioning. For example, the book shows how the relationship between DNA mechanical properties and the sequence specificity of DNA-protein binding can be analyzed quantitatively by using our current knowledge of the physical and structural properties of DNA. Theoretical models and experimental methods in the field are critically considered to enable the reader to engage effectively with the current scientific literature on the physical properties of DNA.

  5. Biophysical properties and computational modeling of calcium spikes in serotonergic neurons of the dorsal raphe nucleus.

    Science.gov (United States)

    Tuckwell, Henry C

    2013-06-01

    Serotonergic neurons of the dorsal raphe nuclei, with their extensive innervation of nearly the whole brain have important modulatory effects on many cognitive and physiological processes. They play important roles in clinical depression and other psychiatric disorders. In order to quantify the effects of serotonergic transmission on target cells it is desirable to construct computational models and to this end these it is necessary to have details of the biophysical and spike properties of the serotonergic neurons. Here several basic properties are reviewed with data from several studies since the 1960s to the present. The quantities included are input resistance, resting membrane potential, membrane time constant, firing rate, spike duration, spike and afterhyperpolarization (AHP) amplitude, spike threshold, cell capacitance, soma and somadendritic areas. The action potentials of these cells are normally triggered by a combination of sodium and calcium currents which may result in autonomous pacemaker activity. We here analyse the mechanisms of high-threshold calcium spikes which have been demonstrated in these cells the presence of TTX (tetrodotoxin). The parameters for calcium dynamics required to give calcium spikes are quite different from those for regular spiking which suggests the involvement of restricted parts of the soma-dendritic surface as has been found, for example, in hippocampal neurons. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Biochemical and biophysical characterization of the transmissible gastroenteritis coronavirus fusion core

    International Nuclear Information System (INIS)

    Ma Guangpeng; Feng Youjun; Gao Feng; Wang Jinzi; Liu Cheng; Li Yijing

    2005-01-01

    Transmissible gastroenteritis coronavirus (TGEV) is one of the most destructive agents, responsible for the enteric infections that are lethal for suckling piglets, causing enormous economic loss to the porcine fostering industry every year. Although it has been known that TGEV spiker protein is essential for the viral entry for many years, the detail knowledge of the TGEV fusion protein core is still very limited. Here, we report that TGEV fusion core (HR1-SGGRGG-HR2), in vitro expressed in GST prokaryotic expression system, shares the typical properties of the trimer of coiled-coil heterodimer (six α-helix bundle), which has been confirmed by a combined series of biochemical and biophysical evidences including size exclusion chromatography (gel-filtration), chemical crossing, and circular diagram. The 3D homologous structure model presents its most likely structure, extremely similar to those of the coronaviruses documented. Taken together, TGEV spiker protein belongs to the class I fusion protein, characterized by the existence of two heptad-repeat (HR) regions, HR1 and HR2, and the present knowledge about the truncated TGEV fusion protein core may facilitate in the design of the small molecule or polypeptide drugs targeting the membrane fusion between TGEV and its host

  7. The effect of natural and synthetic fatty acids on membrane structure, microdomain organization, cellular functions and human health.

    Science.gov (United States)

    Ibarguren, Maitane; López, David J; Escribá, Pablo V

    2014-06-01

    This review deals with the effects of synthetic and natural fatty acids on the biophysical properties of membranes, and on their implication on cell function. Natural fatty acids are constituents of more complex lipids, like triacylglycerides or phospholipids, which are used by cells to store and obtain energy, as well as for structural purposes. Accordingly, natural and synthetic fatty acids may modify the structure of the lipid membrane, altering its microdomain organization and other physical properties, and provoking changes in cell signaling. Therefore, by modulating fatty acids it is possible to regulate the structure of the membrane, influencing the cell processes that are reliant on this structure and potentially reverting pathological cell dysfunctions that may provoke cancer, diabetes, hypertension, Alzheimer's and Parkinson's disease. The so-called Membrane Lipid Therapy offers a strategy to regulate the membrane composition through drug administration, potentially reverting pathological processes by re-adapting cell membrane structure. Certain fatty acids and their synthetic derivatives are described here that may potentially be used in such therapies, where the cell membrane itself can be considered as a target to combat disease. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Influence of Glucose Deprivation on Membrane Potentials of Plasma Membranes, Mitochondria and Synaptic Vesicles in Rat Brain Synaptosomes.

    Science.gov (United States)

    Hrynevich, Sviatlana V; Pekun, Tatyana G; Waseem, Tatyana V; Fedorovich, Sergei V

    2015-06-01

    Hypoglycemia can cause neuronal cell death similar to that of glutamate-induced cell death. In the present paper, we investigated the effect of glucose removal from incubation medium on changes of mitochondrial and plasma membrane potentials in rat brain synaptosomes using the fluorescent dyes DiSC3(5) and JC-1. We also monitored pH gradients in synaptic vesicles and their recycling by the fluorescent dye acridine orange. Glucose deprivation was found to cause an inhibition of K(+)-induced Ca(2+)-dependent exocytosis and a shift of mitochondrial and plasma membrane potentials to more positive values. The sensitivity of these parameters to the energy deficit caused by the removal of glucose showed the following order: mitochondrial membrane potential > plasma membrane potential > pH gradient in synaptic vesicles. The latter was almost unaffected by deprivation compared with the control. The pH-dependent dye acridine orange was used to investigate synaptic vesicle recycling. However, the compound's fluorescence was shown to be enhanced also by the mixture of mitochondrial toxins rotenone (10 µM) and oligomycin (5 µg/mL). This means that acridine orange can presumably be partially distributed in the intermembrane space of mitochondria. Glucose removal from the incubation medium resulted in a 3.7-fold raise of acridine orange response to rotenone + oligomycin suggesting a dramatic increase in the mitochondrial pH gradient. Our results suggest that the biophysical characteristics of neuronal presynaptic endings do not favor excessive non-controlled neurotransmitter release in case of hypoglycemia. The inhibition of exocytosis and the increase of the mitochondrial pH gradient, while preserving the vesicular pH gradient, are proposed as compensatory mechanisms.

  9. Biophysical approach to low back pain: a pilot report

    Czech Academy of Sciences Publication Activity Database

    Foletti, A.; Pokorný, Jiří

    2015-01-01

    Roč. 34, č. 2 (2015), s. 156-159 ISSN 1536-8378 Institutional support: RVO:67985882 Keywords : Bioelectromagnetic medicine * Biophysical therapy * Coherence domains Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 1.208, year: 2015

  10. Interaction of a peptide derived from C-terminus of human TRPA1 channel with model membranes mimicking the inner leaflet of the plasma membrane.

    Science.gov (United States)

    Witschas, Katja; Jobin, Marie-Lise; Korkut, Dursun Nizam; Vladan, Maria Magdalena; Salgado, Gilmar; Lecomte, Sophie; Vlachova, Viktorie; Alves, Isabel D

    2015-05-01

    The transient receptor potential ankyrin 1 channel (TRPA1) belongs to the TRP cation channel superfamily that responds to a panoply of stimuli such as changes in temperature, calcium levels, reactive oxygen and nitrogen species and lipid mediators among others. The TRP superfamily has been implicated in diverse pathological states including neurodegenerative disorders, kidney diseases, inflammation, pain and cancer. The intracellular C-terminus is an important regulator of TRP channel activity. Studies with this and other TRP superfamily members have shown that the C-terminus association with lipid bilayer alters channel sensitivity and activation, especially interactions occurring through basic residues. Nevertheless, it is not yet clear how this process takes place and which regions in the C-terminus would be responsible for such membrane recognition. With that in mind, herein the first putative membrane interacting region of the C-terminus of human TRPA1, (corresponding to a 29 residue peptide, IAEVQKHASLKRIAMQVELHTSLEKKLPL) named H1 due to its potential helical character was chosen for studies of membrane interaction. The affinity of H1 to lipid membranes, H1 structural changes occurring upon this interaction as well as effects of this interaction in lipid organization and integrity were investigated using a biophysical approach. Lipid models systems composed of zwitterionic and anionic lipids, namely those present in the lipid membrane inner leaflet, where H1 is prone to interact, where used. The study reveals a strong interaction and affinity of H1 as well as peptide structuration especially with membranes containing anionic lipids. Moreover, the interactions and peptide structure adoption are headgroup specific. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Selective Interaction of a Cationic Polyfluorene with Model Lipid Membranes: Anionic versus Zwitterionic Lipids

    Directory of Open Access Journals (Sweden)

    Zehra Kahveci

    2014-03-01

    Full Text Available This paper explores the interaction mechanism between the conjugated polyelectrolyte {[9,9-bis(6'-N,N,N-trimethylammoniumhexyl]fluorene-phenylene}bromide (HTMA-PFP and model lipid membranes. The study was carried out using different biophysical techniques, mainly fluorescence spectroscopy and microscopy. Results show that despite the preferential interaction of HTMA-PFP with anionic lipids, HTMA-PFP shows affinity for zwitterionic lipids; although the interaction mechanism is different as well as HTMA-PFP’s final membrane location. Whilst the polyelectrolyte is embedded within the lipid bilayer in the anionic membrane, it remains close to the surface, forming aggregates that are sensitive to the physical state of the lipid bilayer in the zwitterionic system. The different interaction mechanism is reflected in the polyelectrolyte fluorescence spectrum, since the maximum shifts to longer wavelengths in the zwitterionic system. The intrinsic fluorescence of HTMA-PFP was used to visualize the interaction between polymer and vesicles via fluorescence microscopy, thanks to its high quantum yield and photostability. This technique allows the selectivity of the polyelectrolyte and higher affinity for anionic membranes to be observed. The results confirmed the appropriateness of using HTMA-PFP as a membrane fluorescent marker and suggest that, given its different behaviour towards anionic and zwitterionic membranes, HTMA-PFP could be used for selective recognition and imaging of bacteria over mammalian cells.

  12. Membrane fusion between baculovirus budded virus-enveloped particles and giant liposomes generated using a droplet-transfer method for the incorporation of recombinant membrane proteins.

    Science.gov (United States)

    Nishigami, Misako; Mori, Takaaki; Tomita, Masahiro; Takiguchi, Kingo; Tsumoto, Kanta

    2017-07-01

    Giant proteoliposomes are generally useful as artificial cell membranes in biochemical and biophysical studies, and various procedures for their preparation have been reported. We present here a novel preparation technique that involves the combination of i) cell-sized lipid vesicles (giant unilamellar vesicles, GUVs) that are generated using the droplet-transfer method, where lipid monolayer-coated water-in-oil microemulsion droplets interact with oil/water interfaces to form enclosed bilayer vesicles, and ii) budded viruses (BVs) of baculovirus (Autographa californica nucleopolyhedrovirus) that express recombinant transmembrane proteins on their envelopes. GP64, a fusogenic glycoprotein on viral envelopes, is activated by weak acids and is thought to cause membrane fusion with liposomes. Using confocal laser scanning microscopy (CLSM), we observed that the single giant liposomes fused with octadecyl rhodamine B chloride (R18)-labeled wild-type BV envelopes with moderate leakage of entrapped soluble compounds (calcein), and the fusion profile depended on the pH of the exterior solution: membrane fusion occurred at pH ∼4-5. We further demonstrated that recombinant transmembrane proteins, a red fluorescent protein (RFP)-tagged GPCR (corticotropin-releasing hormone receptor 1, CRHR1) and envelope protein GP64 could be partly incorporated into membranes of the individual giant liposomes with a reduction of the pH value, though there were also some immobile fluorescent spots observed on their circumferences. This combination may be useful for preparing giant proteoliposomes containing the desired membranes and inner phases. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Why Do Fast-Growing Bacteria Enter Overflow Metabolism? Testing the Membrane Real Estate Hypothesis.

    Science.gov (United States)

    Szenk, Mariola; Dill, Ken A; de Graff, Adam M R

    2017-08-23

    Bacteria and other cells show a puzzling behavior. At high growth rates, E. coli switch from respiration (which is ATP-efficient) to using fermentation for additional ATP (which is inefficient). This overflow metabolism results in a several-fold decrease in ATP produced per glucose molecule provided as food. By integrating diverse types of experimental data into a simple biophysical model, we give evidence that this onset is the result of the membrane real estate hypothesis: Fast growth drives cells to be bigger, reducing their surface-to-volume ratios. This decreases the membrane area available for respiratory proteins despite growing demand, causing increased crowding. Only when respiratory proteins reach their crowding limit does the cell activate fermentation, since fermentation allows faster ATP production per unit membrane area. Surface limitation thus creates a Pareto trade-off between membrane efficiency and ATP yield that links metabolic choice to the size and shape of a bacterial cell. By exploring the predictions that emerge from this trade-off, we show how consideration of molecular structures, energetics, rates, and equilibria can provide important insight into cellular behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Supercritical CO2 induces marked changes in membrane phospholipids composition in Escherichia coli K12.

    Science.gov (United States)

    Tamburini, Sabrina; Anesi, Andrea; Ferrentino, Giovanna; Spilimbergo, Sara; Guella, Graziano; Jousson, Olivier

    2014-06-01

    Supercritical carbon dioxide (SC-CO2) treatment is one of the most promising alternative techniques for pasteurization of both liquid and solid food products. The inhibitory effect of SC-CO2 on bacterial growth has been investigated in different species, but the precise mechanism of action remains unknown. Membrane permeabilization has been proposed to be the first event in SC-CO2-mediated inactivation. Flow cytometry, high performance liquid chromatography–electrospray ionization–mass spectrometry and NMR analyses were performed to investigate the effect of SC-CO2 treatment on membrane lipid profile and membrane permeability in Escherichia coli K12. After 15 min of SC-CO2 treatment at 120 bar and 35 °C, the majority of bacterial cells dissipated their membrane potential (95 %) and lost membrane integrity, as 81 % become partially permeabilized and 18 % fully permeabilized. Membrane permeabilization was associated with a 20 % decrease in bacterial biovolume and to a strong (>50 %) reduction in phosphatidylglycerol (PG) membrane lipids, without altering the fatty acid composition and the degree of unsaturation of acyl chains. PGs are thought to play an important role in membrane stability, by reducing motion of phosphatidylethanolamine (PE) along the membrane bilayer, therefore promoting the formation of inter-lipid hydrogen bonds. In addition, the decrease in intracellular pH induced by SC-CO2 likely alters the chemical properties of phospholipids and the PE/PG ratio. Biophysical effects of SC-CO2 thus cause a strong perturbation of membrane architecture in E. coli, and such alterations are likely associated with its strong inactivation effect.

  15. Biophysical dosimetry using electron paramagnetic resonance in human tooth

    International Nuclear Information System (INIS)

    Khan, R.F.H.; Boreham, D.R.; Rink, W.J.

    2002-01-01

    Accidental dosimetry utilizing radiation induced paramagnetic species in biophysical tissues like teeth is a technique; that can measure the amount of radiation exposure to an individual. The major problem in implementing this technique at low doses is the presence of native organic signal, and various other artifacts produced as a result of sample processing. After a series of experimental trials, we developed an optimum set of rules, which uses high temperature ultrasonic treatment of enamel in KOH, multiple sample rotation during in-cavity measurement of natural and calibrated added irradiations, and dose construction using a backward extrapolation method. By using this we report the successful dose reconstruction in a few of our laboratory samples in 100 mGy range (76.29 ± 30.14) mGy with reasonably low uncertainty. Keywords: biophysical dosimetry, human tooth enamel, low dose measurements, accidental dosimetry (author)

  16. Radiobiology, biochemistry and radiation biophysics at CYLAB

    International Nuclear Information System (INIS)

    Ftacnikova, S.

    1998-01-01

    The Cyclotron Laboratory (CYLAB) should fill the gap in the field of nuclear medicine, radiotherapy, basic research, metrology of ionizing radiation, education and implications of accelerator technology existing today in Slovak Republic. The main planned activities of this facility are in the fields of nuclear medicine (production of radioisotopes for Positron Emission Tomography - PET and for oncology) and radiotherapy (neutron capture therapy, fast neutron therapy and proton therapy). The radiobiological and biophysical research will be closely connected with medical applications, particularly with radiotherapy. Problems to be addressed include the determination of the values of Relative Biological Effectiveness (RBE) for different types of ionizing radiation involved in the therapy, microdosimetric measurements and calculations, which are indispensable in the calculation of the absorbed dose (lineal and specific energy spectra) at the cellular and macromolecular level. Radiation biophysics and medical physics help in creating therapeutic plans for radiotherapy (NCT and fast neutron therapy). In nuclear medicine, in diagnostic and therapeutical procedures it is necessary to assess the biodistribution of radiopharmaceuticals and to calculate doses in target and critical organs and to determine whole body burden - effective equivalent dose for newly developed radiopharmaceuticals

  17. Cellular membrane accommodation of copper-induced oxidative conditions in the coral Seriatopora caliendrum

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chuan-Ho, E-mail: chtang@nmmba.gov.tw [Institute of Marine Biodiversity and Evolutionary Biology, National Dong Hwa University, Pingtung, Taiwan, ROC (China); National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, ROC (China); Lin, Ching-Yu [Institute of Environmental Health, National Taiwan University, Taipei City, Taiwan, ROC (China); Lee, Shu-Hui [Center of General Education, National Kaohsiung Marine University, Kaohsiung, Taiwan, ROC (China); Wang, Wei-Hsien [National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, ROC (China); Department of Marine Biotechnology and Resources and Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC (China)

    2014-03-01

    -phosphatidylcholines were shown to facilitate membrane fusion. Based on the biochemical and biophysical properties of these lipids, the chronic effects of copper, such as coral resistance and growth, can be logically interpreted to result from long-term perturbations in cellular membrane-related functions. In conclusion, the cells of S. caliendrum alter their lipid metabolism and sacrifice fitness to allow the membrane to accommodate copper-induced oxidative situations.

  18. Cellular membrane accommodation of copper-induced oxidative conditions in the coral Seriatopora caliendrum

    International Nuclear Information System (INIS)

    Tang, Chuan-Ho; Lin, Ching-Yu; Lee, Shu-Hui; Wang, Wei-Hsien

    2014-01-01

    -phosphatidylcholines were shown to facilitate membrane fusion. Based on the biochemical and biophysical properties of these lipids, the chronic effects of copper, such as coral resistance and growth, can be logically interpreted to result from long-term perturbations in cellular membrane-related functions. In conclusion, the cells of S. caliendrum alter their lipid metabolism and sacrifice fitness to allow the membrane to accommodate copper-induced oxidative situations

  19. Influence of Cholesterol on the Oxygen Permeability of Membranes: Insight from Atomistic Simulations.

    Science.gov (United States)

    Dotson, Rachel J; Smith, Casey R; Bueche, Kristina; Angles, Gary; Pias, Sally C

    2017-06-06

    Cholesterol is widely known to alter the physical properties and permeability of membranes. Several prior works have implicated cell membrane cholesterol as a barrier to tissue oxygenation, yet a good deal remains to be explained with regard to the mechanism and magnitude of the effect. We use molecular dynamics simulations to provide atomic-resolution insight into the influence of cholesterol on oxygen diffusion across and within the membrane. Our simulations show strong overall agreement with published experimental data, reproducing the shapes of experimental oximetry curves with high accuracy. We calculate the upper-limit transmembrane oxygen permeability of a 1-palmitoyl,2-oleoylphosphatidylcholine phospholipid bilayer to be 52 ± 2 cm/s, close to the permeability of a water layer of the same thickness. With addition of cholesterol, the permeability decreases somewhat, reaching 40 ± 2 cm/s at the near-saturating level of 62.5 mol % cholesterol and 10 ± 2 cm/s in a 100% cholesterol mimic of the experimentally observed noncrystalline cholesterol bilayer domain. These reductions in permeability can only be biologically consequential in contexts where the diffusional path of oxygen is not water dominated. In our simulations, cholesterol reduces the overall solubility of oxygen within the membrane but enhances the oxygen transport parameter (solubility-diffusion product) near the membrane center. Given relatively low barriers to passing from membrane to membrane, our findings support hydrophobic channeling within membranes as a means of cellular and tissue-level oxygen transport. In such a membrane-dominated diffusional scheme, the influence of cholesterol on oxygen permeability is large enough to warrant further attention. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. Ultrasound assessment of the fetal biophysical profile: What does an radiologist need to know?

    International Nuclear Information System (INIS)

    Guimaraes Filho, Helio Antonio; Araujo Junior, Edward; Marcondes Machado Nardozza, Luciano; Linhares Dias da Costa, Lavoisier; Fernandes Moron, Antonio; Mattar, Rosiane

    2008-01-01

    Proposed by Frank Manning about 26 years ago, fetal biophysical profile has been incorporated to the propaedeutics of non-invasive fetal well being assessment in high-risk gestations. Despite the existence of other methods for assessing fetal vitality, as Doppler flowmetry, the biophysical profile continues to be important in estimating the risk of hypoxia and perinatal morbimortality for those fetuses. In the present article, the authors review the regulatory mechanisms of fetal biophysical activities, as well as physiological and pathological factors that interfere with them. The main objective of the study is to discuss the present and important aspects of the method, and the practical applications and interpretation of its findings, in order to help radiologists improve their knowledge in this specific area of fetal ultrasonography

  1. Principles and biophysical applications of single particle super-localization and rotational tracking

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Yan [Iowa State Univ., Ames, IA (United States)

    2013-01-01

    While conventional Single Particle Tracking (SPT) techniques acquire 2D or 3D trajectories of particle probes, we have developed Single Particle Orientation and Rotational Tracking (SPORT) techniques to extract orientation and rotational information. Combined with DIC microscopy, the SPORT technique has been applied in biophysical studies, including membrane diffusion and intracellular transport. The rotational dynamics of nanoparticle vectors on live cell membranes was recorded and its influence on the fate of these nanoparticle vectors was elucidated. The rotational motions of gold nanorods with various surface modifiers were tracked continuously at a temporal resolution of 5 ms under a DIC microscope. We found that the rotational behaviors of gold nanorod vectors are strongly related to their surface charge, specific surface functional groups, and the availability of receptors on cell membranes. The study of rotational Brownian motion of nanoparticles on cell membranes will lead to a better understanding of the mechanisms of drug delivery and provide guidance in designing surface modification strategies for drug delivery vectors under various circumstances. To characterize the rotation mode of surface functionalized gold nanorods on cell membranes, the SPORT technique is combined with the correlation analysis of the bright and dark DIC intensities. The unique capabilities of visualizing and understanding rotational motions of functionalized nanoparticles on live cell membranes allow us to correlate rotational and translational dynamics in unprecedented detail and provide new insights for complex membrane processes, including electrostatic interactions, ligand-receptor binding, and lateral (confined and hopping) diffusion of membrane receptors. Surface-functionalized nanoparticles interact with the membrane in fundamentally different ways and exhibit distinct rotational modes. The early events of particle-membrane approach and attachment are directly visualized

  2. Principles and biophysical applications of single particle super-localization and rotational tracking

    Science.gov (United States)

    Gu, Yan

    While conventional Single Particle Tracking (SPT) techniques acquire 2D or 3D trajectories of particle probes, we have developed Single Particle Orientation and Rotational Tracking (SPORT) techniques to extract orientation and rotational information. Combined with DIC microscopy, the SPORT technique has been applied in biophysical studies, including membrane diffusion and intracellular transport. The rotational dynamics of nanoparticle vectors on live cell membranes was recorded and its influence on the fate of these nanoparticle vectors was elucidated. The rotational motions of gold nanorods with various surface modifiers were tracked continuously at a temporal resolution of 5 ms under a DIC microscope. We found that the rotational behaviors of gold nanorod vectors are strongly related to their surface charge, specific surface functional groups, and the availability of receptors on cell membranes. The study of rotational Brownian motion of nanoparticles on cell membranes will lead to a better understanding of the mechanisms of drug delivery and provide guidance in designing surface modification strategies for drug delivery vectors under various circumstances. To characterize the rotation mode of surface functionalized gold nanorods on cell membranes, the SPORT technique is combined with the correlation analysis of the bright and dark DIC intensities. The unique capabilities of visualizing and understanding rotational motions of functionalized nanoparticles on live cell membranes allow us to correlate rotational and translational dynamics in unprecedented detail and provide new insights for complex membrane processes, including electrostatic interactions, ligand-receptor binding, and lateral (confined and hopping) diffusion of membrane receptors. Surface-functionalized nanoparticles interact with the membrane in fundamentally different ways and exhibit distinct rotational modes. The early events of particle-membrane approach and attachment are directly visualized

  3. RNS60, a charge-stabilized nanostructure saline alters Xenopus Laevis oocyte biophysical membrane properties by enhancing mitochondrial ATP production

    Science.gov (United States)

    Choi, Soonwook; Yu, Eunah; Kim, Duk-Soo; Sugimori, Mutsuyuki; Llinás, Rodolfo R

    2015-01-01

    We have examined the effects of RNS60, a 0.9% saline containing charge-stabilized oxygen nanobubble-based structures. RNS60 is generated by subjecting normal saline to Taylor–Couette–Poiseuille (TCP) flow under elevated oxygen pressure. This study, implemented in Xenopus laevis oocytes, addresses both the electrophysiological membrane properties and parallel biological processes in the cytoplasm. Intracellular recordings from defolliculated X. laevis oocytes were implemented in: (1) air oxygenated standard Ringer's solution, (2) RNS60-based Ringer's solution, (3) RNS10.3 (TCP-modified saline without excess oxygen)-based Ringer's, and (4) ONS60 (saline containing high pressure oxygen without TCP modification)-based Ringer's. RNS60-based Ringer's solution induced membrane hyperpolarization from the resting membrane potential. This effect was prevented by: (1) ouabain (a blocker of the sodium/potassium ATPase), (2) rotenone (a mitochondrial electron transfer chain inhibitor preventing usable ATP synthesis), and (3) oligomycin A (an inhibitor of ATP synthase) indicating that RNS60 effects intracellular ATP levels. Increased intracellular ATP levels following RNS60 treatment were directly demonstrated using luciferin/luciferase photon emission. These results indicate that RNS60 alters intrinsic the electrophysiological properties of the X. laevis oocyte membrane by increasing mitochondrial-based ATP synthesis. Ultrastructural analysis of the oocyte cytoplasm demonstrated increased mitochondrial length in the presence of RNS60-based Ringer's solution. It is concluded that the biological properties of RNS60 relate to its ability to optimize ATP synthesis. PMID:25742953

  4. Seminal Fluid Analysis And Biophysical Profile: Findings And ...

    African Journals Online (AJOL)

    Seminal Fluid Analysis And Biophysical Profile: Findings And Relevance In Infertile Males In Ilorin, Nigeria. EK Oghagbon, AAG Jimoh, SA Adebisi. Abstract. To determine if there was a bearing of body mass index (BMI) on male infertility, a cross-sectional study of males of infertile couples, attending our infertility clinic was ...

  5. An ethnographic study: Becoming a physics expert in a biophysics research group

    Science.gov (United States)

    Rodriguez, Idaykis

    Expertise in physics has been traditionally studied in cognitive science, where physics expertise is understood through the difference between novice and expert problem solving skills. The cognitive perspective of physics experts only create a partial model of physics expertise and does not take into account the development of physics experts in the natural context of research. This dissertation takes a social and cultural perspective of learning through apprenticeship to model the development of physics expertise of physics graduate students in a research group. I use a qualitative methodological approach of an ethnographic case study to observe and video record the common practices of graduate students in their biophysics weekly research group meetings. I recorded notes on observations and conduct interviews with all participants of the biophysics research group for a period of eight months. I apply the theoretical framework of Communities of Practice to distinguish the cultural norms of the group that cultivate physics expert practices. Results indicate that physics expertise is specific to a topic or subfield and it is established through effectively publishing research in the larger biophysics research community. The participant biophysics research group follows a learning trajectory for its students to contribute to research and learn to communicate their research in the larger biophysics community. In this learning trajectory students develop expert member competencies to learn to communicate their research and to learn the standards and trends of research in the larger research community. Findings from this dissertation expand the model of physics expertise beyond the cognitive realm and add the social and cultural nature of physics expertise development. This research also addresses ways to increase physics graduate student success towards their PhD. and decrease the 48% attrition rate of physics graduate students. Cultivating effective research

  6. Representing biophysical landscape interactions in soil models by bridging disciplines and scales.

    Science.gov (United States)

    van der Ploeg, M. J.; Carranza, C.; Teixeira da Silva, R.; te Brake, B.; Baartman, J.; Robinson, D.

    2017-12-01

    The combination of climate change, population growth and soil threats including carbon loss, biodiversity decline and erosion, increasingly confront the global community (Schwilch et al., 2016). One major challenge in studying processes involved in soil threats, landscape resilience, ecosystem stability, sustainable land management and resulting economic consequences, is that it is an interdisciplinary field (Pelletier et al., 2012). Less stringent scientific disciplinary boundaries are therefore important (Liu et al., 2007), because as a result of disciplinary focus, ambiguity may arise on the understanding of landscape interactions. This is especially true in the interaction between a landscape's physical and biological processes (van der Ploeg et al. 2012). Biophysical landscape interactions are those biotic and abiotic processes in a landscape that have an influence on the developments within and evolution of a landscape. An important aspect in biophysical landscape interactions is the differences in scale related to the various processes that play a role in these systems. Moreover, the interplay between the physical landscape and the occurring vegetation, which often co-evolve, and the resulting heterogeneity and emerging patterns are the reason why it is so challenging to establish a theoretical basis to describe biophysical processes in landscapes (e.g. te Brake et al. 2013, Robinson et al. 2016). Another complicating factor is the response of vegetation to changing environmental conditions, including a possible, and often unknown, time-lag (e.g. Metzger et al., 2009). An integrative description for modelling biophysical interactions has been a long standing goal in soil science (Vereecken et al., 2016). We need the development of soil models that are more focused on networks, connectivity and feedbacks incorporating the most important aspects of our detailed mechanistic modelling (Paola & Leeder, 2011). Additionally, remote sensing measurement techniques

  7. Remote sensing of the Canadian Arctic: Modelling biophysical variables

    Science.gov (United States)

    Liu, Nanfeng

    It is anticipated that Arctic vegetation will respond in a variety of ways to altered temperature and precipitation patterns expected with climate change, including changes in phenology, productivity, biomass, cover and net ecosystem exchange. Remote sensing provides data and data processing methodologies for monitoring and assessing Arctic vegetation over large areas. The goal of this research was to explore the potential of hyperspectral and high spatial resolution multispectral remote sensing data for modelling two important Arctic biophysical variables: Percent Vegetation Cover (PVC) and the fraction of Absorbed Photosynthetically Active Radiation (fAPAR). A series of field experiments were conducted to collect PVC and fAPAR at three Canadian Arctic sites: (1) Sabine Peninsula, Melville Island, NU; (2) Cape Bounty Arctic Watershed Observatory (CBAWO), Melville Island, NU; and (3) Apex River Watershed (ARW), Baffin Island, NU. Linear relationships between biophysical variables and Vegetation Indices (VIs) were examined at different spatial scales using field spectra (for the Sabine Peninsula site) and high spatial resolution satellite data (for the CBAWO and ARW sites). At the Sabine Peninsula site, hyperspectral VIs exhibited a better performance for modelling PVC than multispectral VIs due to their capacity for sampling fine spectral features. The optimal hyperspectral bands were located at important spectral features observed in Arctic vegetation spectra, including leaf pigment absorption in the red wavelengths and at the red-edge, leaf water absorption in the near infrared, and leaf cellulose and lignin absorption in the shortwave infrared. At the CBAWO and ARW sites, field PVC and fAPAR exhibited strong correlations (R2 > 0.70) with the NDVI (Normalized Difference Vegetation Index) derived from high-resolution WorldView-2 data. Similarly, high spatial resolution satellite-derived fAPAR was correlated to MODIS fAPAR (R2 = 0.68), with a systematic

  8. Quantitative analysis of self-association and mobility of annexin A4 at the plasma membrane.

    Science.gov (United States)

    Crosby, Kevin C; Postma, Marten; Hink, Mark A; Zeelenberg, Christiaan H C; Adjobo-Hermans, Merel J W; Gadella, Theodorus W J

    2013-05-07

    Annexins, found in most eukaryotic species, are cytosolic proteins that are able to bind negatively-charged phospholipids in a calcium-dependent manner. Annexin A4 (AnxA4) has been implicated in diverse cellular processes, including the regulation of exocytosis and ion-transport; however, its precise mechanistic role is not fully understood. AnxA4 has been shown to aggregate on lipid layers upon Ca(2+) binding in vitro, a characteristic that may be critical for its function. We have utilized advanced fluorescence microscopy to discern details on the mobility and self-assembly of AnxA4 after Ca(2+) influx at the plasma membrane in living cells. Total internal reflection microscopy in combination with Förster resonance energy transfer reveals that there is a delay between initial plasma membrane binding and the beginning of self-assembly and this process continues after the cytoplasmic pool has completely relocated. Number-and-brightness analysis suggests that the predominant membrane bound mobile form of the protein is trimeric. There also exists a pool of AnxA4 that forms highly immobile aggregates at the membrane. Fluorescence recovery after photobleaching suggests that the relative proportion of these two forms varies and is correlated with membrane morphology. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. Biophysical constraints on leaf expansion in a tall conifer.

    Science.gov (United States)

    Fredrick C. Meinzer; Barbara J. Bond; Jennifer A. Karanian

    2008-01-01

    The physiological mechanisms responsible for reduced extension growth as trees increase in height remain elusive. We evaluated biophysical constraints on leaf expansion in old-growth Douglas-fir (Psuedotsuga menziesii (Mirb.) Franco) trees. Needle elongation rates, plastic and elastic extensibility, bulk leaf water, (L...

  10. Biophysics and cancer

    CERN Document Server

    Nicolini, Claudio

    1986-01-01

    Since the early times of the Greek philosophers Leucippus and Democritus, and later of the Roman philosopher Lucretius, a simple, fundamental idea emerged that brought the life sciences into the realm of the physical sciences. Atoms, after various interactions, were assumed to acquire stable configurations that corresponded either to the living or to the inanimate world. This simple and unitary theory, which has evolved in successive steps to our present time, remarkably maintained its validity despite several centuries of alternative vicissitudes, and is the foundation of modern biophysics. Some of the recent developments of this ancient idea are the discovery of the direct relationship between spatial structures and chemical activity of such molecules as methane and benzene, and the later discovery of the three-dimensional structure of double-helical DNA, and of its relationship with biological activity. The relationship between the structure of various macromolecules and the function of living cells was on...

  11. Membrane-mediated oligomerization of G protein coupled receptors and its implications for GPCR function

    Directory of Open Access Journals (Sweden)

    Stefan Gahbauer

    2016-10-01

    Full Text Available The dimerization or even oligomerization of G protein coupled receptors (GPCRs causes ongoing, controversial debates about its functional role and the coupled biophysical, biochemical or biomedical implications. A continously growing number of studies hints to a relation between oligomerization and function of GPCRs and strengthens the assumption that receptor assembly plays a key role in the regulation of protein function. Additionally, progress in the structural analysis of GPCR-G protein and GPCR-ligand interactions allows to distinguish between actively functional and non-signalling complexes. Recent findings further suggest that the surrounding membrane, i.e. its lipid composition may modulate the preferred dimerization interface and as a result the abundance of distinct dimeric conformations. In this review, the association of GPCRs and the role of the membrane in oligomerization will be discussed. An overview of the different reported oligomeric interfaces is provided and their capability for signaling discussed. The currently available data is summarized with regard to the formation of GPCR oligomers, their structures and dependency on the membrane microenvironment as well as the coupling of oligomerization to receptor function.

  12. Improving hemocompatibility of membranes for extracorporeal membrane oxygenators by grafting nonthrombogenic polymer brushes

    Czech Academy of Sciences Publication Activity Database

    Obstals, F.; Vorobii, M.; Riedel, Tomáš; de los Santos Pereira, Andres; Bruns, M.; Singh, S.; Rodriguez-Emmenegger, C.

    2018-01-01

    Roč. 18, č. 3 (2018), s. 1-11, č. článku 1700359. ISSN 1616-5187 R&D Projects: GA ČR(CZ) GBP205/12/G118 Institutional support: RVO:61389013 Keywords : ECMO * hemocompatibility * nonthrombogenic Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 3.238, year: 2016

  13. Rubber particle proteins, HbREF and HbSRPP, show different interactions with model membranes.

    Science.gov (United States)

    Berthelot, Karine; Lecomte, Sophie; Estevez, Yannick; Zhendre, Vanessa; Henry, Sarah; Thévenot, Julie; Dufourc, Erick J; Alves, Isabel D; Peruch, Frédéric

    2014-01-01

    The biomembrane surrounding rubber particles from the hevea latex is well known for its content of numerous allergen proteins. HbREF (Hevb1) and HbSRPP (Hevb3) are major components, linked on rubber particles, and they have been shown to be involved in rubber synthesis or quality (mass regulation), but their exact function is still to be determined. In this study we highlighted the different modes of interactions of both recombinant proteins with various membrane models (lipid monolayers, liposomes or supported bilayers, and multilamellar vesicles) to mimic the latex particle membrane. We combined various biophysical methods (polarization-modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS)/ellipsometry, attenuated-total reflectance Fourier-transform infrared (ATR-FTIR), solid-state nuclear magnetic resonance (NMR), plasmon waveguide resonance (PWR), fluorescence spectroscopy) to elucidate their interactions. Small rubber particle protein (SRPP) shows less affinity than rubber elongation factor (REF) for the membranes but displays a kind of "covering" effect on the lipid headgroups without disturbing the membrane integrity. Its structure is conserved in the presence of lipids. Contrarily, REF demonstrates higher membrane affinity with changes in its aggregation properties, the amyloid nature of REF, which we previously reported, is not favored in the presence of lipids. REF binds and inserts into membranes. The membrane integrity is highly perturbed, and we suspect that REF is even able to remove lipids from the membrane leading to the formation of mixed micelles. These two homologous proteins show affinity to all membrane models tested but neatly differ in their interacting features. This could imply differential roles on the surface of rubber particles. © 2013.

  14. Biophysical Evaluation of Food Decontamination Effects on Tissue and Bacteria

    DEFF Research Database (Denmark)

    Andersen, Ann Zahle; Duelund, Lars; Brewer, Jonathan

    2011-01-01

    Traditionally, the effects and efficiency of food surface decontamination processes, such as chlorine washing, radiation, or heating, have been evaluated by sensoric analysis and colony-forming unit (CFU) counts of surface swabs or carcass rinses. These methods suffice when determining probable...... consumer responses or meeting legislative contamination limits. However, in the often very costly, optimization process of a new method, more quantitative and unbiased results are invaluable. In this study, we employed a biophysical approach for the investigation of qualitative and quantitative changes...... that there are no contradictions between data obtained by either approach. However, the biophysical methods draw a much more nuanced picture of the effects and efficiency of the investigated decontamination method, revealing, e.g., an exponential dose/response relationship between SonoSteam® treatment time and changes in collagen...

  15. A biotic video game smart phone kit for formal and informal biophysics education

    Science.gov (United States)

    Kim, Honesty; Lee, Seung Ah; Riedel-Kruse, Ingmar

    2015-03-01

    Novel ways for formal and informal biophysics education are important. We present a low-cost biotic game design kit that incorporates microbial organisms into an interactive gaming experience: A 3D-printable microscope containing four LEDs controlled by a joystick enable human players to provide directional light stimuli to the motile single-celled organism Euglena gracilis. These cellular behaviors are displayed on the integrated smart phone. Real time cell-tracking couples these cells into interactive biotic video game play, i.e., the human player steers Euglena to play soccer with virtual balls and goals. The player's learning curve in mastering this fun game is intrinsically coupled to develop a deeper knowledge about Euglena's cell morphology and the biophysics of its phototactic behavior. This kit is dual educational - via construction and via play - and it provides an engaging theme for a formal biophysics devices class as well as to be presented in informal outreach activities; its low cost and open soft- and hardware should enable wide adoption.

  16. Simultaneous Characterization of Instantaneous Young’s Modulus and Specific Membrane Capacitance of Single Cells Using a Microfluidic System

    Directory of Open Access Journals (Sweden)

    Yang Zhao

    2015-01-01

    Full Text Available This paper presents a microfluidics-based approach capable of continuously characterizing instantaneous Young’s modulus (Einstantaneous and specific membrane capacitance (Cspecific membrane of suspended single cells. In this method, cells were aspirated through a constriction channel while the cellular entry process into the constriction channel was recorded using a high speed camera and the impedance profiles at two frequencies (1 kHz and 100 kHz were simultaneously measured by a lock-in amplifier. Numerical simulations were conducted to model cellular entry process into the constriction channel, focusing on two key parameters: instantaneous aspiration length (Linstantaneous and transitional aspiration length (Ltransitional, which was further translated to Einstantaneous. An equivalent distribution circuit model for a cell travelling in the constriction channel was used to determine Cspecific membrane. A non-small-cell lung cancer cell line 95C (n = 354 was used to evaluate this technique, producing Einstantaneous of 2.96 ± 0.40 kPa and Cspecific membrane of 1.59 ± 0.28 μF/cm2. As a platform for continuous and simultaneous characterization of cellular Einstantaneous and Cspecific membrane, this approach can facilitate a more comprehensive understanding of cellular biophysical properties.

  17. Vesicles mimicking normal and cancer cell membranes exhibit differential responses to the cell-penetrating peptide Pep-1.

    Science.gov (United States)

    Almarwani, Bashiyar; Phambu, Esther Nzuzi; Alexander, Christopher; Nguyen, Ha Aimee T; Phambu, Nsoki; Sunda-Meya, Anderson

    2018-06-01

    The cell-penetrating peptide (CPP) Pep-1 presents a great potential in drug delivery due to its intrinsic property to cross plasma membrane. However, its mechanism of entry into the cell remains unresolved. In this study, we compare the selectivity of Pep-1 towards vesicles mimicking normal and cancer cell membranes. The interaction was performed in a wide range of peptide-to-lipid molar ratios using infrared (IR), fluorescence, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. At low peptide concentration, fluorescence experiments show that lipid-phosphatidylserine (PS) seems to enable Pep-1 translocation into cancer cell membrane as evidenced by the blue shift of its maximal emission wavelength. DSC data show that Pep-1 induces segregation of lipids. At high peptide concentration, IR data indicate that the interaction of Pep-1 is relatively stronger with normal cell membrane than with cancer cell membrane through the phosphate groups, while the interaction is weaker with normal cell membrane than with cancer cell membrane through the carbonyl groups. TGA and DSC data reveal that vesicles of normal cell membrane are thermally more stable than vesicles of cancer cell membrane. This suggests that the additional lipid PS included in cancer cell membrane has a destabilizing effect on the membrane structure. SEM images reveal that Pep-1 form superstructures including spherical particles and fibrils in the presence of both model membranes. PS seems to enhance peptide transport across cellular membranes. The biophysical techniques in this study provide valuable insights into the properties of CPPs in drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Biophysical approach to low back pain: a pilot report.

    Science.gov (United States)

    Foletti, Alberto; Pokorný, Jiry

    2015-01-01

    Since biophysical treatment has been reported to be effective in the general management of pain, we decided to assess the specific effect and treatment duration of this therapeutic strategy in low back pain. We were interested in verifying the possibility that a single clinical procedure could reduce pain and improve patients' quality of life within a period of three months. An Electromagnetic Information Transfer Through Aqueous System was employed to record endogenous therapeutic signals from each individual using an electromagnetic recording device (Med Select 729). A highly significant reduction in the Roland Morris low back pain and disability questionnaire score was observed after 3 months following a single biophysical intervention (11.83 ± 6 at baseline versus 2.3 ± 3.25 at 3 months, p < 0.0001). This preliminary report provides further evidence of the theoretical implications and clinical applications of Quantum Electro Dynamic concepts in biology and medicine.

  19. Quantum-Sequencing: Biophysics of quantum tunneling through nucleic acids

    Science.gov (United States)

    Casamada Ribot, Josep; Chatterjee, Anushree; Nagpal, Prashant

    2014-03-01

    Tunneling microscopy and spectroscopy has extensively been used in physical surface sciences to study quantum tunneling to measure electronic local density of states of nanomaterials and to characterize adsorbed species. Quantum-Sequencing (Q-Seq) is a new method based on tunneling microscopy for electronic sequencing of single molecule of nucleic acids. A major goal of third-generation sequencing technologies is to develop a fast, reliable, enzyme-free single-molecule sequencing method. Here, we present the unique ``electronic fingerprints'' for all nucleotides on DNA and RNA using Q-Seq along their intrinsic biophysical parameters. We have analyzed tunneling spectra for the nucleotides at different pH conditions and analyzed the HOMO, LUMO and energy gap for all of them. In addition we show a number of biophysical parameters to further characterize all nucleobases (electron and hole transition voltage and energy barriers). These results highlight the robustness of Q-Seq as a technique for next-generation sequencing.

  20. A note on the roles of quantum and mechanical models in social biophysics.

    Science.gov (United States)

    Takahashi, Taiki; Kim, Song-Ju; Naruse, Makoto

    2017-11-01

    Recent advances in the applications of quantum models into various disciplines such as cognitive science, social sciences, economics, and biology witnessed enormous achievements and possible future progress. In this paper, we propose one of the most promising directions in the applications of quantum models: the combination of quantum and mechanical models in social biophysics. The possible resulting discipline may be called as experimental quantum social biophysics and could foster our understandings of the relationships between the society and individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Biophysical processes in the Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Mc; Murtugudde, R.; Vialard, J.; Vinayachandran, P.N.; Wiggert, J.D.; Hood, R.R.; Shankar, D.; Shetye, S.R.

    Ocean Biogeochemical Processes and Ecological Variability Geophysical Monograph Series 185 Copyright 200� by the American Geophysical Union. 10.102�/2008GM000768 Biophysical Processes in the Indian Ocean J. P. McCreary, 1 R. Murtugudde, 2 J. Vialard, 3...) also plots the upper-layer thickness, h 1 , from the model of McCreary et al. [1��3] (hereinafter referred to as MKM); h 1 simulates the structure of the top of the actual thermocline reasonably well, except that it is somewhat too thin from 5...

  2. The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini.

    Directory of Open Access Journals (Sweden)

    Aljona Gaiko-Shcherbak

    Full Text Available The biophysical properties of the basement membrane that surrounds human breast glands are poorly understood, but are thought to be decisive for normal organ function and malignancy. Here, we characterize the breast gland basement membrane with a focus on molecule permeation and mechanical stability, both crucial for organ function. We used well-established and nature-mimicking MCF10A acini as 3D cell model for human breast glands, with ether low- or highly-developed basement membrane scaffolds. Semi-quantitative dextran tracer (3 to 40 kDa experiments allowed us to investigate the basement membrane scaffold as a molecule diffusion barrier in human breast acini in vitro. We demonstrated that molecule permeation correlated positively with macromolecule size and intriguingly also with basement membrane development state, revealing a pore size of at least 9 nm. Notably, an intact collagen IV mesh proved to be essential for this permeation function. Furthermore, we performed ultra-sensitive atomic force microscopy to quantify the response of native breast acini and of decellularized basement membrane shells against mechanical indentation. We found a clear correlation between increasing acinar force resistance and basement membrane formation stage. Most important native acini with highly-developed basement membranes as well as cell-free basement membrane shells could both withstand physiologically relevant loads (≤ 20 nN without loss of structural integrity. In contrast, low-developed basement membranes were significantly softer and more fragile. In conclusion, our study emphasizes the key role of the basement membrane as conductor of acinar molecule influx and mechanical stability of human breast glands, which are fundamental for normal organ function.

  3. Hierarchy and Interactions in Environmental Interfaces Regarded as Biophysical Complex Systems

    Science.gov (United States)

    Mihailovic, Dragutin T.; Balaz, Igor

    The field of environmental sciences is abundant with various interfaces and is the right place for the application of new fundamental approaches leading towards a better understanding of environmental phenomena. For example, following the definition of environmental interface by Mihailovic and Balaž [23], such interface can be placed between: human or animal bodies and surrounding air, aquatic species and water and air around them, and natural or artificially built surfaces (vegetation, ice, snow, barren soil, water, urban communities) and the atmosphere. Complex environmental interface systems are open and hierarchically organised, interactions between their constituent parts are nonlinear, and the interaction with the surrounding environment is noisy. These systems are therefore very sensitive to initial conditions, deterministic external perturbations and random fluctuations always present in nature. The study of noisy non-equilibrium processes is fundamental for modelling the dynamics of environmental interface systems and for understanding the mechanisms of spatio-temporal pattern formation in contemporary environmental sciences, particularly in environmental fluid mechanics. In modelling complex biophysical systems one of the main tasks is to successfully create an operative interface with the external environment. It should provide a robust and prompt translation of the vast diversity of external physical and/or chemical changes into a set of signals, which are "understandable" for an organism. Although the establishment of organisation in any system is of crucial importance for its functioning, it should not be forgotten that in biophysical systems we deal with real-life problems where a number of other conditions should be reached in order to put the system to work. One of them is the proper supply of the system by the energy. Therefore, we will investigate an aspect of dynamics of energy flow based on the energy balance equation. The energy as well as

  4. Tetraspanins and Transmembrane Adaptor Proteins As Plasma Membrane Organizers-Mast Cell Case.

    Science.gov (United States)

    Halova, Ivana; Draber, Petr

    2016-01-01

    The plasma membrane contains diverse and specialized membrane domains, which include tetraspanin-enriched domains (TEMs) and transmembrane adaptor protein (TRAP)-enriched domains. Recent biophysical, microscopic, and functional studies indicated that TEMs and TRAP-enriched domains are involved in compartmentalization of physicochemical events of such important processes as immunoreceptor signal transduction and chemotaxis. Moreover, there is evidence of a cross-talk between TEMs and TRAP-enriched domains. In this review we discuss the presence and function of such domains and their crosstalk using mast cells as a model. The combined data based on analysis of selected mast cell-expressed tetraspanins [cluster of differentiation (CD)9, CD53, CD63, CD81, CD151)] or TRAPs [linker for activation of T cells (LAT), non-T cell activation linker (NTAL), and phosphoprotein associated with glycosphingolipid-enriched membrane microdomains (PAG)] using knockout mice or specific antibodies point to a diversity within these two families and bring evidence of the important roles of these molecules in signaling events. An example of this diversity is physical separation of two TRAPs, LAT and NTAL, which are in many aspects similar but show plasma membrane location in different microdomains in both non-activated and activated cells. Although our understanding of TEMs and TRAP-enriched domains is far from complete, pharmaceutical applications of the knowledge about these domains are under way.

  5. Toxoplasma gondii: Biochemical and biophysical characterization of recombinant soluble dense granule proteins GRA2 and GRA6

    International Nuclear Information System (INIS)

    Bittame, Amina; Effantin, Grégory; Pètre, Graciane; Ruffiot, Pauline; Travier, Laetitia; Schoehn, Guy; Weissenhorn, Winfried; Cesbron-Delauw, Marie-France; Gagnon, Jean; Mercier, Corinne

    2015-01-01

    The most prominent structural feature of the parasitophorous vacuole (PV) in which the intracellular parasite Toxoplasma gondii proliferates is a membranous nanotubular network (MNN), which interconnects the parasites and the PV membrane. The MNN function remains unclear. The GRA2 and GRA6 proteins secreted from the parasite dense granules into the PV have been implicated in the MNN biogenesis. Amphipathic alpha-helices (AAHs) predicted in GRA2 and an alpha-helical hydrophobic domain predicted in GRA6 have been proposed to be responsible for their membrane association, thereby potentially molding the MMN in its structure. Here we report an analysis of the recombinant proteins (expressed in detergent-free conditions) by circular dichroism, which showed that full length GRA2 displays an alpha-helical secondary structure while recombinant GRA6 and GRA2 truncated of its AAHs are mainly random coiled. Dynamic light scattering and transmission electron microscopy showed that recombinant GRA6 and truncated GRA2 constitute a homogenous population of small particles (6–8 nm in diameter) while recombinant GRA2 corresponds to 2 populations of particles (∼8–15 nm and up to 40 nm in diameter, respectively). The unusual properties of GRA2 due to its AAHs are discussed. - Highlights: • Toxoplasma gondii: soluble GRA2 forms 2 populations of particles. • T. gondii: the dense granule protein GRA2 folds intrinsically as an alpha-helix. • T. gondii: monomeric soluble GRA6 forms particles of 6–8 nm in diameter. • T. gondii: monomeric soluble GRA6 is random coiled. • Unusual biophysical properties of the dense granule protein GRA2 from T. gondii

  6. Toxoplasma gondii: Biochemical and biophysical characterization of recombinant soluble dense granule proteins GRA2 and GRA6

    Energy Technology Data Exchange (ETDEWEB)

    Bittame, Amina [CNRS, UMR 5163, 38042 Grenoble (France); Université Grenoble Alpes, 38042 Grenoble (France); Effantin, Grégory [Université Grenoble Alpes, Institut de Biologie Structurale (IBS), 38044 Grenoble (France); CNRS, IBS, 38044 Grenoble (France); CEA, IBS, 38044 Grenoble (France); Unit for Virus Host-Cell Interactions (UVHCI), UMI 3265 (UJF-EMBL-CNRS), 38027 Grenoble (France); Pètre, Graciane; Ruffiot, Pauline; Travier, Laetitia [CNRS, UMR 5163, 38042 Grenoble (France); Université Grenoble Alpes, 38042 Grenoble (France); Schoehn, Guy; Weissenhorn, Winfried [Université Grenoble Alpes, Institut de Biologie Structurale (IBS), 38044 Grenoble (France); CNRS, IBS, 38044 Grenoble (France); CEA, IBS, 38044 Grenoble (France); Unit for Virus Host-Cell Interactions (UVHCI), UMI 3265 (UJF-EMBL-CNRS), 38027 Grenoble (France); Cesbron-Delauw, Marie-France; Gagnon, Jean [CNRS, UMR 5163, 38042 Grenoble (France); Université Grenoble Alpes, 38042 Grenoble (France); Mercier, Corinne, E-mail: corinne.mercier@ujf-grenoble.fr [CNRS, UMR 5163, 38042 Grenoble (France); Université Grenoble Alpes, 38042 Grenoble (France)

    2015-03-27

    The most prominent structural feature of the parasitophorous vacuole (PV) in which the intracellular parasite Toxoplasma gondii proliferates is a membranous nanotubular network (MNN), which interconnects the parasites and the PV membrane. The MNN function remains unclear. The GRA2 and GRA6 proteins secreted from the parasite dense granules into the PV have been implicated in the MNN biogenesis. Amphipathic alpha-helices (AAHs) predicted in GRA2 and an alpha-helical hydrophobic domain predicted in GRA6 have been proposed to be responsible for their membrane association, thereby potentially molding the MMN in its structure. Here we report an analysis of the recombinant proteins (expressed in detergent-free conditions) by circular dichroism, which showed that full length GRA2 displays an alpha-helical secondary structure while recombinant GRA6 and GRA2 truncated of its AAHs are mainly random coiled. Dynamic light scattering and transmission electron microscopy showed that recombinant GRA6 and truncated GRA2 constitute a homogenous population of small particles (6–8 nm in diameter) while recombinant GRA2 corresponds to 2 populations of particles (∼8–15 nm and up to 40 nm in diameter, respectively). The unusual properties of GRA2 due to its AAHs are discussed. - Highlights: • Toxoplasma gondii: soluble GRA2 forms 2 populations of particles. • T. gondii: the dense granule protein GRA2 folds intrinsically as an alpha-helix. • T. gondii: monomeric soluble GRA6 forms particles of 6–8 nm in diameter. • T. gondii: monomeric soluble GRA6 is random coiled. • Unusual biophysical properties of the dense granule protein GRA2 from T. gondii.

  7. Linking biophysical models and public preferences for ecosystem service assessments: a case study for the Southern Rocky Mountains

    Science.gov (United States)

    Bagstad, Kenneth J.; Reed, James; Semmens, Darius J.; Sherrouse, Ben C.; Troy, Austin

    2016-01-01

    Through extensive research, ecosystem services have been mapped using both survey-based and biophysical approaches, but comparative mapping of public values and those quantified using models has been lacking. In this paper, we mapped hot and cold spots for perceived and modeled ecosystem services by synthesizing results from a social-values mapping study of residents living near the Pike–San Isabel National Forest (PSI), located in the Southern Rocky Mountains, with corresponding biophysically modeled ecosystem services. Social-value maps for the PSI were developed using the Social Values for Ecosystem Services tool, providing statistically modeled continuous value surfaces for 12 value types, including aesthetic, biodiversity, and life-sustaining values. Biophysically modeled maps of carbon sequestration and storage, scenic viewsheds, sediment regulation, and water yield were generated using the Artificial Intelligence for Ecosystem Services tool. Hotspots for both perceived and modeled services were disproportionately located within the PSI’s wilderness areas. Additionally, we used regression analysis to evaluate spatial relationships between perceived biodiversity and cultural ecosystem services and corresponding biophysical model outputs. Our goal was to determine whether publicly valued locations for aesthetic, biodiversity, and life-sustaining values relate meaningfully to results from corresponding biophysical ecosystem service models. We found weak relationships between perceived and biophysically modeled services, indicating that public perception of ecosystem service provisioning regions is limited. We believe that biophysical and social approaches to ecosystem service mapping can serve as methodological complements that can advance ecosystem services-based resource management, benefitting resource managers by showing potential locations of synergy or conflict between areas supplying ecosystem services and those valued by the public.

  8. Effects of LiDAR point density, sampling size and height threshold on estimation accuracy of crop biophysical parameters.

    Science.gov (United States)

    Luo, Shezhou; Chen, Jing M; Wang, Cheng; Xi, Xiaohuan; Zeng, Hongcheng; Peng, Dailiang; Li, Dong

    2016-05-30

    Vegetation leaf area index (LAI), height, and aboveground biomass are key biophysical parameters. Corn is an important and globally distributed crop, and reliable estimations of these parameters are essential for corn yield forecasting, health monitoring and ecosystem modeling. Light Detection and Ranging (LiDAR) is considered an effective technology for estimating vegetation biophysical parameters. However, the estimation accuracies of these parameters are affected by multiple factors. In this study, we first estimated corn LAI, height and biomass (R2 = 0.80, 0.874 and 0.838, respectively) using the original LiDAR data (7.32 points/m2), and the results showed that LiDAR data could accurately estimate these biophysical parameters. Second, comprehensive research was conducted on the effects of LiDAR point density, sampling size and height threshold on the estimation accuracy of LAI, height and biomass. Our findings indicated that LiDAR point density had an important effect on the estimation accuracy for vegetation biophysical parameters, however, high point density did not always produce highly accurate estimates, and reduced point density could deliver reasonable estimation results. Furthermore, the results showed that sampling size and height threshold were additional key factors that affect the estimation accuracy of biophysical parameters. Therefore, the optimal sampling size and the height threshold should be determined to improve the estimation accuracy of biophysical parameters. Our results also implied that a higher LiDAR point density, larger sampling size and height threshold were required to obtain accurate corn LAI estimation when compared with height and biomass estimations. In general, our results provide valuable guidance for LiDAR data acquisition and estimation of vegetation biophysical parameters using LiDAR data.

  9. Modelling benthic biophysical drivers of ecosystem structure and biogeochemical response

    Science.gov (United States)

    Stephens, Nicholas; Bruggeman, Jorn; Lessin, Gennadi; Allen, Icarus

    2016-04-01

    The fate of carbon deposited at the sea floor is ultimately decided by biophysical drivers that control the efficiency of remineralisation and timescale of carbon burial in sediments. Specifically, these drivers include bioturbation through ingestion and movement, burrow-flushing and sediment reworking, which enhance vertical particulate transport and solute diffusion. Unfortunately, these processes are rarely satisfactorily resolved in models. To address this, a benthic model that explicitly describes the vertical position of biology (e.g., habitats) and biogeochemical processes is presented that includes biological functionality and biogeochemical response capturing changes in ecosystem structure, benthic-pelagic fluxes and biodiversity on inter-annual timescales. This is demonstrated by the model's ability to reproduce temporal variability in benthic infauna, vertical pore water nutrients and pelagic-benthic solute fluxes compared to in-situ data. A key advance is the replacement of bulk parameterisation of bioturbation by explicit description of the bio-physical processes responsible. This permits direct comparison with observations and determination of key parameters in experiments. Crucially, the model resolves the two-way interaction between sediment biogeochemistry and ecology, allowing exploration of the benthic response to changing environmental conditions, the importance of infaunal functional traits in shaping benthic ecological structure and the feedback the resulting bio-physical processes exert on pore water nutrient profiles. The model is actively being used to understand shelf sea carbon cycling, the response of the benthos to climatic change, food provision and other societal benefits.

  10. Developing a protocol for managing the biophysical condition of a ...

    African Journals Online (AJOL)

    Their function will focus on the overall management of water resources on a ... for the integrated management of the biophysical component of a catchment, with ... and implement a protocol which will combine and integrate the knowledge of ...

  11. Mapping the local organization of cell membranes using excitation-polarization-resolved confocal fluorescence microscopy.

    Science.gov (United States)

    Kress, Alla; Wang, Xiao; Ranchon, Hubert; Savatier, Julien; Rigneault, Hervé; Ferrand, Patrick; Brasselet, Sophie

    2013-07-02

    Fluorescence anisotropy and linear dichroism imaging have been widely used for imaging biomolecular orientational distributions in protein aggregates, fibrillar structures of cells, and cell membranes. However, these techniques do not give access to complete orientational order information in a whole image, because their use is limited to parts of the sample where the average orientation of molecules is known a priori. Fluorescence anisotropy is also highly sensitive to depolarization mechanisms such as those induced by fluorescence energy transfer. A fully excitation-polarization-resolved fluorescence microscopy imaging that relies on the use of a tunable incident polarization and a nonpolarized detection is able to circumvent these limitations. We have developed such a technique in confocal epifluorescence microscopy, giving access to new regions of study in the complex and heterogeneous molecular organization of cell membranes. Using this technique, we demonstrate morphological changes at the subdiffraction scale in labeled COS-7 cell membranes whose cytoskeleton is perturbed. Molecular orientational order is also seen to be affected by cholesterol depletion, reflecting the strong interplay between lipid-packing regions and their nearby cytoskeleton. This noninvasive optical technique can reveal local organization in cell membranes when used as a complement to existing methods such as generalized polarization. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  12. A new automated technique for the reconstitution of hydrophobic proteins into planar bilayer membranes. Studies of human recombinant uncoupling protein 1

    Czech Academy of Sciences Publication Activity Database

    Beck, V.; Jabůrek, Martin; Breen, E. P.; Porter, R. K.; Ježek, Petr; Pohl, E. E.

    2006-01-01

    Roč. 1757, č. 5-6 (2006), s. 474-479 ISSN 0005-2728 R&D Projects: GA AV ČR(CZ) IAA5011106; GA MŠk(CZ) 1P05ME794 Grant - others:Deutsche Forschungsgemeinschaft(DE) Po-524/2-2; Deutsche Forschungsgemeinschaft(DE) 436 TSE 113/44/0-1 Institutional research plan: CEZ:AV0Z50110509 Keywords : artificial membranes * uncoupling protein-1 Subject RIV: BO - Biophysics Impact factor: 4.237, year: 2006

  13. Elementary Energy Transfer Pathways in Allochromatium vinosum Photosynthetic Membranes.

    Science.gov (United States)

    Lüer, Larry; Carey, Anne-Marie; Henry, Sarah; Maiuri, Margherita; Hacking, Kirsty; Polli, Dario; Cerullo, Giulio; Cogdell, Richard J

    2015-11-03

    Allochromatium vinosum (formerly Chromatium vinosum) purple bacteria are known to adapt their light-harvesting strategy during growth according to environmental factors such as temperature and average light intensity. Under low light illumination or low ambient temperature conditions, most of the LH2 complexes in the photosynthetic membranes form a B820 exciton with reduced spectral overlap with LH1. To elucidate the reason for this light and temperature adaptation of the LH2 electronic structure, we performed broadband femtosecond transient absorption spectroscopy as a function of excitation wavelength in A. vinosum membranes. A target analysis of the acquired data yielded individual rate constants for all relevant elementary energy transfer (ET) processes. We found that the ET dynamics in high-light-grown membranes was well described by a homogeneous model, with forward and backward rate constants independent of the pump wavelength. Thus, the overall B800→B850→B890→ Reaction Center ET cascade is well described by simple triexponential kinetics. In the low-light-grown membranes, we found that the elementary backward transfer rate constant from B890 to B820 was strongly reduced compared with the corresponding constant from B890 to B850 in high-light-grown samples. The ET dynamics of low-light-grown membranes was strongly dependent on the pump wavelength, clearly showing that the excitation memory is not lost throughout the exciton lifetime. The observed pump energy dependence of the forward and backward ET rate constants suggests exciton diffusion via B850→ B850 transfer steps, making the overall ET dynamics nonexponential. Our results show that disorder plays a crucial role in our understanding of low-light adaptation in A. vinosum. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Biophysical properties of the normal-sized aorta in patients with Marfan syndrome: evaluation with MR flow mapping

    NARCIS (Netherlands)

    Groenink, M.; de Roos, A.; Mulder, B. J.; Verbeeten, B.; Timmermans, J.; Zwinderman, A. H.; Spaan, J. A.; van der Wall, E. E.

    2001-01-01

    PURPOSE: To investigate the feasibility of magnetic resonance (MR) flow mapping in the assessment of aortic biophysical properties in patients with Marfan syndrome and to detect differences in biophysical properties in the normal-sized aorta distal to the aortic root between these patients and

  15. A Method Sustaining the Bioelectric, Biophysical, and Bioenergetic Function of Cultured Rabbit Atrial Cells

    OpenAIRE

    Noa Kirschner Peretz; Sofia Segal; Limor Arbel-Ganon; Ronen Ben Jehuda; Ronen Ben Jehuda; Yuval Shemer; Yuval Shemer; Binyamin Eisen; Binyamin Eisen; Moran Davoodi; Ofer Binah; Ofer Binah; Yael Yaniv

    2017-01-01

    Culturing atrial cells leads to a loss in their ability to be externally paced at physiological rates and to maintain their shape. We aim to develop a culture method that sustains the shape of atrial cells along with their biophysical and bioenergetic properties in response to physiological pacing. We hypothesize that adding 2,3-Butanedione 2-monoxime (BDM), which inhibits contraction during the culture period, will preserve these biophysical and bioenergetic properties. Rabbit atrial cells w...

  16. Lysenin Toxin Membrane Insertion Is pH-Dependent but Independent of Neighboring Lysenins.

    Science.gov (United States)

    Munguira, Ignacio L B; Takahashi, Hirohide; Casuso, Ignacio; Scheuring, Simon

    2017-11-07

    Pore-forming toxins form a family of proteins that act as virulence factors of pathogenic bacteria, but similar proteins are found in all kingdoms of life, including the vertebrate immune system. They are secreted as soluble monomers that oligomerize on target membranes in the so-called prepore state; after activation, they insert into the membrane and adopt the pore state. Lysenin is a pore-forming toxin from the earthworm Eisenida foetida, of which both the soluble and membrane-inserted structures are solved. However, the activation and membrane-insertion mechanisms have remained elusive. Here, we used high-speed atomic force microscopy to directly visualize the membrane-insertion mechanism. Changing the environmental pH from pH 7.5 to below pH 6.0 favored membrane insertion. We detected a short α-helix in the soluble structure that comprised three glutamic acids (Glu92, Glu94, and Glu97) that we hypothesized may represent a pH-sensor (as in similar toxins, e.g., Listeriolysin). Mutant lysenin still can form pores, but mutating these glutamic acids to glutamines rendered the toxin pH-insensitive. On the other hand, toxins in the pore state did not favor insertion of neighboring prepores; indeed, pore insertion breaks the hexagonal ordered domains of prepores and separates from neighboring molecules in the membrane. pH-dependent activation of toxins may represent a common feature of pore-forming toxins. High-speed atomic force microscopy with single-molecule resolution at high temporal resolution and the possibility of exchanging buffers during the experiments presents itself as a unique tool for the study of toxin-state conversion. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. Antimycotic activity of fengycin C biosurfactant and its interaction with phosphatidylcholine model membranes.

    Science.gov (United States)

    González-Jaramillo, Lina María; Aranda, Francisco José; Teruel, José Antonio; Villegas-Escobar, Valeska; Ortiz, Antonio

    2017-08-01

    Lipopeptide biosurfactants constitute one of the most promising groups of compounds for the treatment and prevention of fungal diseases in plants. Bacillus subtilis strain EA-CB0015 produces iturin A, fengycin C and surfactin and it has been proven useful for the treatment of black Sigatoka disease in banana plants, an important pathology caused by the fungus Mycosphaerella fijiensis (Morelet). We have found that B. subtilis EA-CB0015 cell free supernatants and purified fractions inhibit M. fijiensis cellular growth. The effect of the purified lipopeptides mentioned above on fungal growth has been also evaluated, observing that iturin A and fengycin C inhibit mycelial growth and ascospore germination, whereas surfactin is not effective. On the hypothesis that the antifungal action of the lipopeptides is associated to their incorporation into biological membranes, ultimately leading to membrane permeabilization, a detailed biophysical study on the interaction of a new isoform of fengycin C with model dipalmitoyphosphatidylcholine (DPPC) membranes has been carried out. Differential scanning calorimetry shows that fengycin C alters the thermotropic phase transitions of DPPC, and is laterally segregated in the fluid bilayer forming domains. Fluorescent probe polarization measurements show that fengycin C does not affect the hydrophobic interior of the membrane. This latter perturbation is concomitant with a strong dehydration of the polar region of DPPC, as shown by FTIR. Fengycin-rich domains, where the surrounding DPPC molecules are highly dehydrated, may well constitute sites of membrane permeabilization leading to a leaky target membrane. These results are a solid support to explain the membrane perturbing action of fengycin, which has been related to its antifungal activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Nanoscale biophysics of the cell

    CERN Document Server

    Ashrafuzzaman, Mohammad

    2018-01-01

    Macroscopic cellular structures and functions are generally investigated using biological and biochemical approaches. But these methods are no longer adequate when one needs to penetrate deep into the small-scale structures and understand their functions. The cell is found to hold various physical structures, molecular machines, and processes that require physical and mathematical approaches to understand and indeed manipulate them. Disorders in general cellular compartments, perturbations in single molecular structures, drug distribution therein, and target specific drug-binding, etc. are mostly physical phenomena. This book will show how biophysics has revolutionized our way of addressing the science and technology of nanoscale structures of cells, and also describes the potential for manipulating the events that occur in them.

  19. Recombinant human melatonin receptor MT1 isolated in mixed detergents shows pharmacology similar to that in mammalian cell membranes.

    Directory of Open Access Journals (Sweden)

    Christel Logez

    Full Text Available The human melatonin MT1 receptor-belonging to the large family of G protein-coupled receptors (GPCRs-plays a key role in circadian rhythm regulation and is notably involved in sleep disorders and depression. Structural and functional information at the molecular level are highly desired for fine characterization of this receptor; however, adequate techniques for isolating soluble MT1 material suitable for biochemical and biophysical studies remain lacking. Here we describe the evaluation of a panel of constructs and host systems for the production of recombinant human MT1 receptors, and the screening of different conditions for their solubilization and purification. Our findings resulted in the establishment of an original strategy using a mixture of Fos14 and CHAPS detergents to extract and purify a recombinant human MT1 from Pichia pastoris membranes. This procedure enabled the recovery of relatively pure, monomeric and ligand-binding active MT1 receptor in the near-milligram range. A comparative study based on extensive ligand-binding characterization highlighted a very close correlation between the pharmacological profiles of MT1 purified from yeast and the same receptor present in mammalian cell membranes. The high quality of the purified MT1 was further confirmed by its ability to activate its cognate Gαi protein partner when reconstituted in lipid discs, thus opening novel paths to investigate this receptor by biochemical and biophysical approaches.

  20. Recombinant human melatonin receptor MT1 isolated in mixed detergents shows pharmacology similar to that in mammalian cell membranes.

    Science.gov (United States)

    Logez, Christel; Berger, Sylvie; Legros, Céline; Banères, Jean-Louis; Cohen, William; Delagrange, Philippe; Nosjean, Olivier; Boutin, Jean A; Ferry, Gilles; Simonin, Frédéric; Wagner, Renaud

    2014-01-01

    The human melatonin MT1 receptor-belonging to the large family of G protein-coupled receptors (GPCRs)-plays a key role in circadian rhythm regulation and is notably involved in sleep disorders and depression. Structural and functional information at the molecular level are highly desired for fine characterization of this receptor; however, adequate techniques for isolating soluble MT1 material suitable for biochemical and biophysical studies remain lacking. Here we describe the evaluation of a panel of constructs and host systems for the production of recombinant human MT1 receptors, and the screening of different conditions for their solubilization and purification. Our findings resulted in the establishment of an original strategy using a mixture of Fos14 and CHAPS detergents to extract and purify a recombinant human MT1 from Pichia pastoris membranes. This procedure enabled the recovery of relatively pure, monomeric and ligand-binding active MT1 receptor in the near-milligram range. A comparative study based on extensive ligand-binding characterization highlighted a very close correlation between the pharmacological profiles of MT1 purified from yeast and the same receptor present in mammalian cell membranes. The high quality of the purified MT1 was further confirmed by its ability to activate its cognate Gαi protein partner when reconstituted in lipid discs, thus opening novel paths to investigate this receptor by biochemical and biophysical approaches.

  1. Structural basis for plant plasma membrane protein dynamics and organization into functional nanodomains.

    Science.gov (United States)

    Gronnier, Julien; Crowet, Jean-Marc; Habenstein, Birgit; Nasir, Mehmet Nail; Bayle, Vincent; Hosy, Eric; Platre, Matthieu Pierre; Gouguet, Paul; Raffaele, Sylvain; Martinez, Denis; Grelard, Axelle; Loquet, Antoine; Simon-Plas, Françoise; Gerbeau-Pissot, Patricia; Der, Christophe; Bayer, Emmanuelle M; Jaillais, Yvon; Deleu, Magali; Germain, Véronique; Lins, Laurence; Mongrand, Sébastien

    2017-07-31

    Plasma Membrane is the primary structure for adjusting to ever changing conditions. PM sub-compartmentalization in domains is thought to orchestrate signaling. Yet, mechanisms governing membrane organization are mostly uncharacterized. The plant-specific REMORINs are proteins regulating hormonal crosstalk and host invasion. REMs are the best-characterized nanodomain markers via an uncharacterized moiety called REMORIN C-terminal Anchor. By coupling biophysical methods, super-resolution microscopy and physiology, we decipher an original mechanism regulating the dynamic and organization of nanodomains. We showed that targeting of REMORIN is independent of the COP-II-dependent secretory pathway and mediated by PI4P and sterol. REM-CA is an unconventional lipid-binding motif that confers nanodomain organization. Analyses of REM-CA mutants by single particle tracking demonstrate that mobility and supramolecular organization are critical for immunity. This study provides a unique mechanistic insight into how the tight control of spatial segregation is critical in the definition of PM domain necessary to support biological function.

  2. Biophysical characterization of GPCR oligomerization

    DEFF Research Database (Denmark)

    Mathiasen, Signe

    level, and revealed the existence of several dimerization interfaces, each with specific kinetics. Finally we investigated how a property of the membrane solubilizing GPCRs affected oligomerization. We observed a dramatic decrease in oligomer stability with increasing geometrical membrane curvature. We...

  3. Coupling Biophysical and Socioeconomic Models for Coral Reef Systems in Quintana Roo, Mexican Caribbean

    Directory of Open Access Journals (Sweden)

    Jessica Melbourne-Thomas

    2011-09-01

    Full Text Available Transdisciplinary approaches that consider both socioeconomic and biophysical processes are central to understanding and managing rapid change in coral reef systems worldwide. To date, there have been limited attempts to couple the two sets of processes in dynamic models for coral reefs, and these attempts are confined to reef systems in developed countries. We present an approach to coupling existing biophysical and socioeconomic models for coral reef systems in the Mexican state of Quintana Roo. The biophysical model is multiscale, using dynamic equations to capture local-scale ecological processes on individual reefs, with reefs connected at regional scales by the ocean transport of larval propagules. The agent-based socioeconomic model simulates changes in tourism, fisheries, and urbanization in the Quintana Roo region. Despite differences in the formulation and currencies of the two models, we were able to successfully modify and integrate them to synchronize and define information flows and feedbacks between them. A preliminary evaluation of the coupled model system indicates that the model gives reasonable predictions for fisheries and ecological variables and can be used to examine scenarios for future social-ecological change in Quintana Roo. We provide recommendations for where efforts might usefully be focused in future attempts to integrate models of biophysical and socioeconomic processes, based on the limitations of our coupled system.

  4. Winnowing and Flocculation in Bio-physical Cohesive Substrate: A Flume Experimental and Estuarine Study

    Science.gov (United States)

    Ye, L.; Parsons, D. R.; Manning, A. J.

    2016-12-01

    Cohesive sediment, or mud, is ubiquitously found in most aqueous environments, such as coasts and estuaries. The study of cohesive sediment behaviors requires the synchronous description of mutual interactions of grains (e.g., winnowing and flocculation), their physical properties (e.g., grain size) and also the ambient water. Herein, a series of flume experiments (14 runs) with different substrate mixtures of sand-clay-EPS (Extracellular Polymeric Substrates: secreted by aquatic microorganisms) are combined with an estuarine field survey (Dee estuary, NW England) to investigate the behavior of suspensions over bio-physical cohesive substrates. The experimental results indicate that winnowing and flocculation occur pervasively in bio-physical cohesive flow systems. Importantly however, the evolution of the bed and bedform dynamics and hence turbulence production can be lower when cohesivity is high. The estuarine survey also revealed that the bio-physical cohesion provided by both the clay and microorganism fractions in the bed, that pervasively exists in many natural estuarine systems, plays a significant role in controlling the interactions between bed substrate and sediment suspension and deposition, including controlling processes such as sediment winnowing, flocculation and re-deposition. Full understanding of these processes are essential in advancing sediment transport modelling and prediction studies across natural estuarine systems and the work will report on an improved conceptual model for sediment sorting deposition in bio-physical cohesive substrates.

  5. Comparative proteome analysis reveals pathogen specific outer membrane proteins of Leptospira.

    Science.gov (United States)

    Dhandapani, Gunasekaran; Sikha, Thoduvayil; Rana, Aarti; Brahma, Rahul; Akhter, Yusuf; Gopalakrishnan Madanan, Madathiparambil

    2018-04-10

    Proteomes of pathogenic Leptospira interrogans and L. borgpetersenii and the saprophytic L. biflexa were filtered through computational tools to identify Outer Membrane Proteins (OMPs) that satisfy the required biophysical parameters for their presence on the outer membrane. A total of 133, 130, and 144 OMPs were identified in L. interrogans, L. borgpetersenii, and L. biflexa, respectively, which forms approximately 4% of proteomes. A holistic analysis of transporting and pathogenic characteristics of OMPs together with Clusters of Orthologous Groups (COGs) among the OMPs and their distribution across 3 species was made and put forward a set of 21 candidate OMPs specific to pathogenic leptospires. It is also found that proteins homologous to the candidate OMPs were also present in other pathogenic species of leptospires. Six OMPs from L. interrogans and 2 from L. borgpetersenii observed to have similar COGs while those were not found in any intermediate or saprophytic forms. These OMPs appears to have role in infection and pathogenesis and useful for anti-leptospiral strategies. © 2018 Wiley Periodicals, Inc.

  6. Anti-pulmonary fibrotic activity of salvianolic acid B was screened by a novel method based on the cyto-biophysical properties

    International Nuclear Information System (INIS)

    Liu, Miao; Zheng, Mingjing; Xu, Hanying; Liu, Lianqing; Li, Yanchun; Xiao, Wei; Li, Jianchun; Ma, Enlong

    2015-01-01

    Various methods have been used to evaluate anti-fibrotic activity of drugs. However, most of them are complicated, labor-intensive and lack of efficiency. This study was intended to develop a rapid method for anti-fibrotic drugs screening based on biophysical properties. A549 cells in vitro were stimulated with transforming growth factor-β1 (TGF-β1), and fibrogenesis was confirmed by conventional immunological assays. Meanwhile, the alterations of cyto-biophysical properties including morphology, roughness and stiffness were measured utilizing atomic force microscopy (AFM). It was found that fibrogenesis was accompanied with changes of cellular biophysical properties. TGF-β1-stimulated A549 cells became remarkably longer, rougher and stiffer than the control. Then, the effect of N-acetyl-L-cysteine (NAC) as a positive drug on ameliorating fibrogenesis in TGF-β1-stimulated A549 cells was verified respectively by immunological and biophysical markers. The result of Principal Component Analysis showed that stiffness was a leading index among all biophysical markers during fibrogenesis. Salvianolic acid B (SalB), a natural anti-oxidant, was detected by AFM to protect TGF-β1-stimulated A549 cells against stiffening. Then, SalB treatment was provided in preventive mode on a rat model of bleomycin (BLM) -induced pulmonary fibrosis. The results showed that SalB treatment significantly ameliorated BLM-induced histological alterations, blocked collagen accumulations and reduced α-SMA expression in lung tissues. All these results revealed the anti-pulmonary fibrotic activity of SalB. Detection of cyto-biophysical properties were therefore recommended as a rapid method for anti-pulmonary fibrotic drugs screening. - Highlights: • Fibrogenesis was accompanied with the changes of cyto-biophysical properties. • Cyto-biophysical properties could be markers for anti-fibrotic drugs screening. • Stiffness is a leading index among all biophysical markers. • SalB was

  7. Anti-pulmonary fibrotic activity of salvianolic acid B was screened by a novel method based on the cyto-biophysical properties

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Miao; Zheng, Mingjing; Xu, Hanying [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016 (China); Liu, Lianqing [Shenyang Institute of Automation China Academy of Sciences, Shenyang, 110016 (China); Li, Yanchun [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016 (China); Xiao, Wei [Jiangsu Kanion Pharmaceutical Co., Ltd., Nanjing, 222001 (China); Li, Jianchun, E-mail: lijianchun0317@sina.com.cn [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016 (China); Ma, Enlong, E-mail: enlong_ma2014@hotmail.com [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016 (China); Jiangsu Kanion Pharmaceutical Co., Ltd., Nanjing, 222001 (China)

    2015-12-04

    Various methods have been used to evaluate anti-fibrotic activity of drugs. However, most of them are complicated, labor-intensive and lack of efficiency. This study was intended to develop a rapid method for anti-fibrotic drugs screening based on biophysical properties. A549 cells in vitro were stimulated with transforming growth factor-β1 (TGF-β1), and fibrogenesis was confirmed by conventional immunological assays. Meanwhile, the alterations of cyto-biophysical properties including morphology, roughness and stiffness were measured utilizing atomic force microscopy (AFM). It was found that fibrogenesis was accompanied with changes of cellular biophysical properties. TGF-β1-stimulated A549 cells became remarkably longer, rougher and stiffer than the control. Then, the effect of N-acetyl-L-cysteine (NAC) as a positive drug on ameliorating fibrogenesis in TGF-β1-stimulated A549 cells was verified respectively by immunological and biophysical markers. The result of Principal Component Analysis showed that stiffness was a leading index among all biophysical markers during fibrogenesis. Salvianolic acid B (SalB), a natural anti-oxidant, was detected by AFM to protect TGF-β1-stimulated A549 cells against stiffening. Then, SalB treatment was provided in preventive mode on a rat model of bleomycin (BLM) -induced pulmonary fibrosis. The results showed that SalB treatment significantly ameliorated BLM-induced histological alterations, blocked collagen accumulations and reduced α-SMA expression in lung tissues. All these results revealed the anti-pulmonary fibrotic activity of SalB. Detection of cyto-biophysical properties were therefore recommended as a rapid method for anti-pulmonary fibrotic drugs screening. - Highlights: • Fibrogenesis was accompanied with the changes of cyto-biophysical properties. • Cyto-biophysical properties could be markers for anti-fibrotic drugs screening. • Stiffness is a leading index among all biophysical markers. • SalB was

  8. Mass spectrometry for the biophysical characterization of therapeutic monoclonal antibodies.

    Science.gov (United States)

    Zhang, Hao; Cui, Weidong; Gross, Michael L

    2014-01-21

    Monoclonal antibodies (mAbs) are powerful therapeutics, and their characterization has drawn considerable attention and urgency. Unlike small-molecule drugs (150-600 Da) that have rigid structures, mAbs (∼150 kDa) are engineered proteins that undergo complicated folding and can exist in a number of low-energy structures, posing a challenge for traditional methods in structural biology. Mass spectrometry (MS)-based biophysical characterization approaches can provide structural information, bringing high sensitivity, fast turnaround, and small sample consumption. This review outlines various MS-based strategies for protein biophysical characterization and then reviews how these strategies provide structural information of mAbs at the protein level (intact or top-down approaches), peptide, and residue level (bottom-up approaches), affording information on higher order structure, aggregation, and the nature of antibody complexes. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  9. Tetraspanins and Transmembrane Adaptor Proteins as Plasma Membrane Organizers – Mast Cell Case

    Directory of Open Access Journals (Sweden)

    Ivana eHalova

    2016-05-01

    Full Text Available The plasma membrane contains diverse and specialized membrane domains, which include tetraspanin-enriched domains (TEMs and transmembrane adaptor protein (TRAP-enriched domains. Recent biophysical, microscopic and functional studies indicated that TEMs and TRAP-enriched domains are involved in compartmentalization of physicochemical events of such important processes as immunoreceptor signal transduction and chemotaxis. Moreover, there is evidence of a cross-talk between TEMs and TRAP-enriched domains. In this review we discuss the presence and function of such domains and their crosstalk using mast cells as a model. The combined data based on analysis of selected mast cell-expressed tetraspanins [cluster of differentiation (CD9, CD53, CD63, CD81, CD151] or TRAPs [linker for activation of T cells (LAT, non-T cell activation linker (NTAL, and phosphoprotein associated with glycosphingolipid-enriched membrane microdomains (PAG] using knockout mice or specific antibodies point to a diversity within these two families and bring evidence of the important roles of these molecules in signaling events. An example of this diversity is physical separation of two TRAPs, LAT and NTAL, which are in many aspects similar but show plasma membrane location in different microdomains in both non-activated and activated cells. Although our understanding of TEMs and TRAP-enriched domains is far from complete, pharmaceutical applications of the knowledge about these domains are under way.

  10. Synchrotron radiation applications in biophysics and medicine

    International Nuclear Information System (INIS)

    Burattini, E.

    1985-01-01

    The peculiar properties of synchrotron radiation are briefly summarized. A short review on the possible applications of synchrotron radiation in two important fields like Biophysics and Medicine is presented. Details are given on experiments both in progress and carried out in many synchrotron radiation facilities, all over the world, using different techniques like X-ray absorption and fluorescence spectroscopy, X-ray fluorescence microanalysis, X-ray microscopy and digital subtraction angiography. Some news about the photon-activation therapy are briefly reported too

  11. Short-Term Memory and Its Biophysical Model

    Science.gov (United States)

    Wang, Wei; Zhang, Kai; Tang, Xiao-wei

    1996-12-01

    The capacity of short-term memory has been studied using an integrate-and-fire neuronal network model. It is found that the storage of events depend on the manner of the correlation between the events, and the capacity is dominated by the value of after-depolarization potential. There is a monotonic increasing relationship between the value of after-depolarization potential and the memory numbers. The biophysics relevance of the network model is discussed and different kinds of the information processes are studied too.

  12. Enhancing the biophysical properties of mRFP1 through incorporation of fluoroproline

    Energy Technology Data Exchange (ETDEWEB)

    Deepankumar, Kanagavel; Nadarajan, Saravanan Prabhu; Ayyadurai, Niraikulam; Yun, Hyungdon, E-mail: hyungdon@ynu.ac.kr

    2013-11-01

    Graphical abstract: Enhancing the biophysical properties of mRFP1 through incorporation of (2S, 4R)-4-fluoroproline at proline residues after mutating non-permissive site Pro63 into Ala. -- Highlights: •We incorporate (4S)-FP into mRFP1 led to insoluble protein. •Whereas, incorporation of (4R)-FP resulted in soluble but lost its fluorescence. •mRFP1-P63A mutant accommodate (4R)-FP and gave soluble protein with fluorescence. •Moreover mRFP1-P63A[(4R)-FP] showed enhanced biophysical properties of protein. -- Abstract: Here we enhanced the stability and biophysical properties of mRFP1 through a combination of canonical and non-canonical amino acid mutagenesis. The global replacement of proline residue with (2S, 4R)-4-fluoroproline [(4R)-FP] into mRFP1 led to soluble protein but lost its fluorescence, whereas (2S, 4S)-4-fluoroproline [(4S)-FP] incorporation resulted in insoluble protein. The bioinformatics analysis revealed that (4R)-FP incorporation at Pro63 caused fluorescence loss due to the steric hindrance of fluorine atom of (4R)-FP with the chromophore. Therefore, Pro63 residue was mutated with the smallest amino acid Ala to maintain non coplanar conformation of the chromophore and helps to retain its fluorescence with (4R)-FP incorporation. The incorporation of (4R)-FP into mRFP1-P63A showed about 2–3-fold enhancement in thermal and chemical stability. The rate of maturation is also greatly accelerated over the presence of (4R)-FP into mRFP1-P63A. Our study showed that a successful enhancement in the biophysical property of mRFP1-P63A[(4R)-FP] using non-canonical amino acid mutagenesis after mutating non-permissive site Pro63 into Ala.

  13. Materials science and biophysics applications at the ISOLDE radioactive ion beam facility

    Energy Technology Data Exchange (ETDEWEB)

    Wahl, U., E-mail: uwahl@itn.pt [Instituto Tecnologico e Nuclear, Estrada Nacional 10, 2686-953 Sacavem (Portugal); Centro de Fisica Nuclear da Universidade de Lisboa, Av. Prof. Gama Pinto 2, 1649-003 Lisboa (Portugal)

    2011-12-15

    The ISOLDE isotope separator facility at CERN provides a variety of radioactive ion beams, currently more than 800 different isotopes from {approx}70 chemical elements. The radioisotopes are produced on-line by nuclear reactions from a 1.4 GeV proton beam with various types of targets, outdiffusion of the reaction products and, if possible, chemically selective ionisation, followed by 60 kV acceleration and mass separation. While ISOLDE is mainly used for nuclear and atomic physics studies, applications in materials science and biophysics account for a significant part (currently {approx}15%) of the delivered beam time, requested by 18 different experiments. The ISOLDE materials science and biophysics community currently consists of {approx}80 scientists from more than 40 participating institutes and 21 countries. In the field of materials science, investigations focus on the study of semiconductors and oxides, with the recent additions of nanoparticles and metals, while the biophysics studies address the toxicity of metal ions in biological systems. The characterisation methods used are typical radioactive probe techniques such as Moessbauer spectroscopy, perturbed angular correlation, emission channeling, and tracer diffusion studies. In addition to these 'classic' methods of nuclear solid state physics, also standard semiconductor analysis techniques such as photoluminescence or deep level transient spectroscopy profit from the application of radioactive isotopes, which helps them to overcome their chemical 'blindness' since the nuclear half life of radioisotopes provides a signal that changes in time with characteristic exponential decay or saturation curves. In this presentation an overview will be given on the recent research activities in materials science and biophysics at ISOLDE, presenting some of the highlights during the last five years, together with a short outlook on the new developments under way.

  14. Enhancing the biophysical properties of mRFP1 through incorporation of fluoroproline

    International Nuclear Information System (INIS)

    Deepankumar, Kanagavel; Nadarajan, Saravanan Prabhu; Ayyadurai, Niraikulam; Yun, Hyungdon

    2013-01-01

    Graphical abstract: Enhancing the biophysical properties of mRFP1 through incorporation of (2S, 4R)-4-fluoroproline at proline residues after mutating non-permissive site Pro63 into Ala. -- Highlights: •We incorporate (4S)-FP into mRFP1 led to insoluble protein. •Whereas, incorporation of (4R)-FP resulted in soluble but lost its fluorescence. •mRFP1-P63A mutant accommodate (4R)-FP and gave soluble protein with fluorescence. •Moreover mRFP1-P63A[(4R)-FP] showed enhanced biophysical properties of protein. -- Abstract: Here we enhanced the stability and biophysical properties of mRFP1 through a combination of canonical and non-canonical amino acid mutagenesis. The global replacement of proline residue with (2S, 4R)-4-fluoroproline [(4R)-FP] into mRFP1 led to soluble protein but lost its fluorescence, whereas (2S, 4S)-4-fluoroproline [(4S)-FP] incorporation resulted in insoluble protein. The bioinformatics analysis revealed that (4R)-FP incorporation at Pro63 caused fluorescence loss due to the steric hindrance of fluorine atom of (4R)-FP with the chromophore. Therefore, Pro63 residue was mutated with the smallest amino acid Ala to maintain non coplanar conformation of the chromophore and helps to retain its fluorescence with (4R)-FP incorporation. The incorporation of (4R)-FP into mRFP1-P63A showed about 2–3-fold enhancement in thermal and chemical stability. The rate of maturation is also greatly accelerated over the presence of (4R)-FP into mRFP1-P63A. Our study showed that a successful enhancement in the biophysical property of mRFP1-P63A[(4R)-FP] using non-canonical amino acid mutagenesis after mutating non-permissive site Pro63 into Ala

  15. Chiropractic biophysics technique: a linear algebra approach to posture in chiropractic.

    Science.gov (United States)

    Harrison, D D; Janik, T J; Harrison, G R; Troyanovich, S; Harrison, D E; Harrison, S O

    1996-10-01

    This paper discusses linear algebra as applied to human posture in chiropractic, specifically chiropractic biophysics technique (CBP). Rotations, reflections and translations are geometric functions studied in vector spaces in linear algebra. These mathematical functions are termed rigid body transformations and are applied to segmental spinal movement in the literature. Review of the literature indicates that these linear algebra concepts have been used to describe vertebral motion. However, these rigid body movers are presented here as applying to the global postural movements of the head, thoracic cage and pelvis. The unique inverse functions of rotations, reflections and translations provide a theoretical basis for making postural corrections in neutral static resting posture. Chiropractic biophysics technique (CBP) uses these concepts in examination procedures, manual spinal manipulation, instrument assisted spinal manipulation, postural exercises, extension traction and clinical outcome measures.

  16. Radiation biophysics in space

    International Nuclear Information System (INIS)

    Buecker, H.; Horneck, G.

    1983-01-01

    In a demonstration experiment bacterium sporules have been exposed to the space vacuum and to the solar radiation field at 254 nm, with the following results: 1) a short vacuum exposition of 1.3 h does not affect the vitality of the sporules, 2) the survival rate of humid sporules after UV-irradiation is consistent with terrestrial control samples, 3) after a simultaneous exposition to vacuum and solar UV-radiation the effect on the sporules is enhanced by a factor of ten as compared to the situation without vaccum exposition. Additional studies in biophysical simulation systems revealed, that the enhanced UV sensitivity is caused by the dehydration of the sporules. By this process the structure of the essential macromolecules in cell, such as DNA and proteins, is modified such that new photo-products can be formed. For these products the cells have no effective repair systems. (AJ) [de

  17. Biophysics of radiation action

    International Nuclear Information System (INIS)

    Dertinger, H.

    1984-01-01

    Understanding the cellular response to ionizing radiation is not only necessary to meet the requirements of radioprotection, but also for medical application of radiation in cancer treatment. In terms of radiobiology, cancer therapy means the selective inactivation of malignant cells without affecting the normal healthy tissue. However, for several physical and biological reasons, this ideal situation is normally not attained. The elaboration of biophysical parameters that could be used to improve the selective sterilization of tumor cells has become one of the main activities of cellular radiobiology during the last two decades. Progress in this field has been facilitated by the development of tissue culture techniques allowing to grow and analyze cells in a synthetic nutrient medium. This chapter describes the physical and biological factors which determine cellular radiosensitivity and which are important to know for better understanding the cellular radiation action, in particular with reference to cancer treatment

  18. Low-Resolution Structure of Detergent-Solubilized Membrane Proteins from Small-Angle Scattering Data.

    Science.gov (United States)

    Koutsioubas, Alexandros

    2017-12-05

    Despite the ever-increasing usage of small-angle scattering as a valuable complementary method in the field of structural biology, applications concerning membrane proteins remain elusive mainly due to experimental challenges and the relative lack of theoretical tools for the treatment of scattering data. This fact adds up to general difficulties encountered also by other established methods (crystallography, NMR) for the study of membrane proteins. Following the general paradigm of ab initio methods for low-resolution restoration of soluble protein structure from small-angle scattering data, we construct a general multiphase model with a set of physical constraints, which, together with an appropriate minimization procedure, gives direct structural information concerning the different components (protein, detergent molecules) of detergent-solubilized membrane protein complexes. Assessment of the method's precision and robustness is evaluated by performing shape restorations from simulated data of a tetrameric α-helical membrane channel (Aquaporin-0) solubilized by n-Dodecyl β-D-Maltoside and from previously published small-angle neutron scattering experimental data of the filamentous hemagglutinin adhesin β-barrel protein transporter solubilized by n-Octyl β-D-glucopyranoside. It is shown that the acquisition of small-angle neutron scattering data at two different solvent contrasts, together with an estimation of detergent aggregation number around the protein, permits the reliable reconstruction of the shape of membrane proteins without the need for any prior structural information. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  19. Perspectives and Plans for Graduate Studies. 16. Biophysics 1974.

    Science.gov (United States)

    Ontario Council on Graduate Studies, Toronto. Advisory Committee on Academic Planning.

    In March, 1973, after a review of the Ontario universities' three-year plans, a provisional embargo was placed on doctoral work in biophysics. A full-scale assessment with outside consultants was not necessary in the case of a provisional embargo. Instead, the method used to remove the embargo was self-study by the discipline group leading to a…

  20. Southwest Ecological Restoration Institutes (SWERI) Biophysical Monitoring Workshop Report

    Science.gov (United States)

    Joseph Seidenberg; Judy Springer; Tessa Nicolet; Mike Battaglia; Christina Vothja

    2009-01-01

    On October 15-16, 2009, the Southwest Ecological Restoration Institutes (SWERI) hosted a workshop in which the participants would 1) build a common understanding of the types of monitoring that are occurring in forested ecosystems of the Southwest; 2) analyze and agree on an efficient, yet robust set of biophysical variables that can be used by land mangers and...

  1. Biophysical and electrochemical studies of protein-nucleic acid interactions

    Czech Academy of Sciences Publication Activity Database

    Bowater, R. P.; Cobb, A:M.; Pivoňková, Hana; Havran, Luděk; Fojta, Miroslav

    2015-01-01

    Roč. 146, č. 5 (2015), s. 723-739 ISSN 0026-9247 R&D Projects: GA ČR(CZ) GBP206/12/G151; GA ČR(CZ) GAP301/11/2076 Institutional support: RVO:68081707 Keywords : ISOTHERMAL TITRATION CALORIMETRY * OSMIUM-TETROXIDE COMPLEXES * SURFACE-PLASMON RESONANCE Subject RIV: BO - Biophysics Impact factor: 1.131, year: 2015

  2. MreB filaments align along greatest principal membrane curvature to orient cell wall synthesis

    Science.gov (United States)

    Szwedziak, Piotr; Wong, Felix; Schaefer, Kaitlin; Izoré, Thierry; Renner, Lars D; Holmes, Matthew J; Sun, Yingjie; Bisson-Filho, Alexandre W; Walker, Suzanne; Amir, Ariel; Löwe, Jan

    2018-01-01

    MreB is essential for rod shape in many bacteria. Membrane-associated MreB filaments move around the rod circumference, helping to insert cell wall in the radial direction to reinforce rod shape. To understand how oriented MreB motion arises, we altered the shape of Bacillus subtilis. MreB motion is isotropic in round cells, and orientation is restored when rod shape is externally imposed. Stationary filaments orient within protoplasts, and purified MreB tubulates liposomes in vitro, orienting within tubes. Together, this demonstrates MreB orients along the greatest principal membrane curvature, a conclusion supported with biophysical modeling. We observed that spherical cells regenerate into rods in a local, self-reinforcing manner: rapidly propagating rods emerge from small bulges, exhibiting oriented MreB motion. We propose that the coupling of MreB filament alignment to shape-reinforcing peptidoglycan synthesis creates a locally-acting, self-organizing mechanism allowing the rapid establishment and stable maintenance of emergent rod shape. PMID:29469806

  3. Differential Interaction of Synthetic Glycolipids with Biomimetic Plasma Membrane Lipids Correlates with the Plant Biological Response.

    Science.gov (United States)

    Nasir, Mehmet Nail; Lins, Laurence; Crowet, Jean-Marc; Ongena, Marc; Dorey, Stephan; Dhondt-Cordelier, Sandrine; Clément, Christophe; Bouquillon, Sandrine; Haudrechy, Arnaud; Sarazin, Catherine; Fauconnier, Marie-Laure; Nott, Katherine; Deleu, Magali

    2017-09-26

    Natural and synthetic amphiphilic molecules including lipopeptides, lipopolysaccharides, and glycolipids are able to induce defense mechanisms in plants. In the present work, the perception of two synthetic C14 rhamnolipids, namely, Alk-RL and Ac-RL, differing only at the level of the lipid tail terminal group have been investigated using biological and biophysical approaches. We showed that Alk-RL induces a stronger early signaling response in tobacco cell suspensions than does Ac-RL. The interactions of both synthetic RLs with simplified biomimetic membranes were further analyzed using experimental and in silico approaches. Our results indicate that the interactions of Alk-RL and Ac-RL with lipids were different in terms of insertion and molecular responses and were dependent on the lipid composition of model membranes. A more favorable insertion of Alk-RL than Ac-RL into lipid membranes is observed. Alk-RL forms more stable molecular assemblies than Ac-RL with phospholipids and sterols. At the molecular level, the presence of sterols tends to increase the RLs' interaction with lipid bilayers, with a fluidizing effect on the alkyl chains. Taken together, our findings suggest that the perception of these synthetic RLs at the membrane level could be related to a lipid-driven process depending on the organization of the membrane and the orientation of the RLs within the membrane and is correlated with the induction of early signaling responses in tobacco cells.

  4. From hadron therapy to cosmic rays: a life in biophysics

    CERN Multimedia

    Christine Sutton

    2014-01-01

    In 1954 – the year CERN was founded – another scientific journey began at what is now the Lawrence Berkeley National Laboratory. Beams of protons from a particle accelerator were used for the first time by John Lawrence – a doctor and the brother of Ernest Lawrence, the physicist after whom the Berkeley lab is named – to treat patients with cancer. For many years, Eleanor Blakely has been one of the leaders of that journey. She visited CERN last week and spoke with the Bulletin about her life in biophysics.   Use of the cylcotron beam to mimic "shooting stars" seen by astronauts. Black hood on subject Cornelius Tobias keeps out light during neutron irradiation experiment at the 184-inch accelerator. Helping to position Tobias in the beam line are (left to right) John Lyman of Biomedical Division, and Ralph Thomas of Health Physics. (Photo courtesy of Lawrence Berkeley National Laboratory.) Interested in biophysics, which was still a new...

  5. Tracking individual membrane proteins and their biochemistry: The power of direct observation.

    Science.gov (United States)

    Barden, Adam O; Goler, Adam S; Humphreys, Sara C; Tabatabaei, Samaneh; Lochner, Martin; Ruepp, Marc-David; Jack, Thomas; Simonin, Jonathan; Thompson, Andrew J; Jones, Jeffrey P; Brozik, James A

    2015-11-01

    The advent of single molecule fluorescence microscopy has allowed experimental molecular biophysics and biochemistry to transcend traditional ensemble measurements, where the behavior of individual proteins could not be precisely sampled. The recent explosion in popularity of new super-resolution and super-localization techniques coupled with technical advances in optical designs and fast highly sensitive cameras with single photon sensitivity and millisecond time resolution have made it possible to track key motions, reactions, and interactions of individual proteins with high temporal resolution and spatial resolution well beyond the diffraction limit. Within the purview of membrane proteins and ligand gated ion channels (LGICs), these outstanding advances in single molecule microscopy allow for the direct observation of discrete biochemical states and their fluctuation dynamics. Such observations are fundamentally important for understanding molecular-level mechanisms governing these systems. Examples reviewed here include the effects of allostery on the stoichiometry of ligand binding in the presence of fluorescent ligands; the observation of subdomain partitioning of membrane proteins due to microenvironment effects; and the use of single particle tracking experiments to elucidate characteristics of membrane protein diffusion and the direct measurement of thermodynamic properties, which govern the free energy landscape of protein dimerization. The review of such characteristic topics represents a snapshot of efforts to push the boundaries of fluorescence microscopy of membrane proteins to the absolute limit. This article is part of the Special Issue entitled 'Fluorescent Tools in Neuropharmacology'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Social and Biophysical Predictors of Public Perceptions of Extreme Fires

    Science.gov (United States)

    Hall, T. E.; Kooistra, C. M.; Paveglio, T.; Gress, S.; Smith, A. M.

    2013-12-01

    To date, what constitutes an 'extreme' fire has been approached separately by biophysical and social scientists. Research on the biophysical characteristics of fires has identified potential dimensions of extremity, including fire size and vegetation mortality. On the social side, factors such as the degree of immediate impact to one's life and property or the extent of social disruption in the community contribute to a perception of extremity. However, some biophysical characteristics may also contribute to perceptions of extremity, including number of simultaneous ignitions, rapidity of fire spread, atypical fire behavior, and intensity of smoke. Perceptions of these impacts can vary within and across communities, but no studies to date have investigated such perceptions in a comprehensive way. In this study, we address the question, to what extent is the magnitude of impact of fires on WUI residents' well-being explained by measurable biophysical characteristics of the fire and subjective evaluations of the personal and community-level impacts of the fire? We bring together diverse strands of psychological theory, including landscape perception, mental models, risk perception, and community studies. The majority of social science research on fires has been in the form of qualitative case studies, and our study is methodologically unique by using a nested design (hierarchical modeling) to enable generalizable conclusions across a wide range of fires and human communities. We identified fires that burned in 2011 or 2012 in the northern Rocky Mountain region that were at least 1,000 acres and that intersected (within 15 km) urban clusters or identified Census places. For fires where an adequately large number of households was located in proximity to the fire, we drew random samples of approximately 150 individuals for each fire. We used a hybrid internet (Qualtrics) and mail survey, following the Dillman method, to measure individual perceptions. We developed two

  7. Past and Present Biophysical Redundancy of Countries as a Buffer to Changes in Food Supply

    Science.gov (United States)

    Fader, Marianela; Rulli, Maria Cristina; Carr, Joel; Dell' Angelo, Jampel; D' Odorico, Paolo; Gephart, Jessica A.; Kummu, Matti; Magliocca, Nicholas; Porkka, Miina; Prell, Christina; hide

    2016-01-01

    Spatially diverse trends in population growth, climate change, industrialization, urbanization and economic development are expected to change future food supply and demand. These changes may affect the suitability of land for food production, implying elevated risks especially for resource constrained, food-importing countries. We present the evolution of biophysical redundancy for agricultural production at country level, from 1992 to 2012. Biophysical redundancy, defined as unused biotic and abiotic environmental resources, is represented by the potential food production of 'spare land', available water resources (i.e., not already used for human activities), as well as production increases through yield gap closure on cultivated areas and potential agricultural areas. In 2012, the biophysical redundancy of 75 (48) countries, mainly in North Africa, Western Europe, the Middle East and Asia, was insufficient to produce the caloric nutritional needs for at least 50% (25%) of their population during a year. Biophysical redundancy has decreased in the last two decades in 102 out of 155 countries, 11 of these went from high to limited redundancy, and nine of these from limited to very low redundancy. Although the variability of the drivers of change across different countries is high, improvements in yield and population growth have a clear impact on the decreases of redundancy towards the very low redundancy category. We took a more detailed look at countries classified as 'Low Income Economies (LIEs)' since they are particularly vulnerable to domestic or external food supply changes, due to their limited capacity to offset for food supply decreases with higher purchasing power on the international market. Currently, nine LIEs have limited or very low biophysical redundancy. Many of these showed a decrease in redundancy over the last two decades, which is not always linked with improvements in per capita food availability.

  8. Past and present biophysical redundancy of countries as a buffer to changes in food supply

    Science.gov (United States)

    Fader, Marianela; Rulli, Maria Cristina; Carr, Joel; Dell'Angelo, Jampel; D'Odorico, Paolo; Gephart, Jessica A.; Kummu, Matti; Magliocca, Nicholas; Porkka, Miina; Prell, Christina; Puma, Michael J.; Ratajczak, Zak; Seekell, David A.; Suweis, Samir; Tavoni, Alessandro

    2016-05-01

    Spatially diverse trends in population growth, climate change, industrialization, urbanization and economic development are expected to change future food supply and demand. These changes may affect the suitability of land for food production, implying elevated risks especially for resource-constrained, food-importing countries. We present the evolution of biophysical redundancy for agricultural production at country level, from 1992 to 2012. Biophysical redundancy, defined as unused biotic and abiotic environmental resources, is represented by the potential food production of ‘spare land’, available water resources (i.e., not already used for human activities), as well as production increases through yield gap closure on cultivated areas and potential agricultural areas. In 2012, the biophysical redundancy of 75 (48) countries, mainly in North Africa, Western Europe, the Middle East and Asia, was insufficient to produce the caloric nutritional needs for at least 50% (25%) of their population during a year. Biophysical redundancy has decreased in the last two decades in 102 out of 155 countries, 11 of these went from high to limited redundancy, and nine of these from limited to very low redundancy. Although the variability of the drivers of change across different countries is high, improvements in yield and population growth have a clear impact on the decreases of redundancy towards the very low redundancy category. We took a more detailed look at countries classified as ‘Low Income Economies (LIEs)’ since they are particularly vulnerable to domestic or external food supply changes, due to their limited capacity to offset for food supply decreases with higher purchasing power on the international market. Currently, nine LIEs have limited or very low biophysical redundancy. Many of these showed a decrease in redundancy over the last two decades, which is not always linked with improvements in per capita food availability.

  9. BIOPHYSICAL PROPERTIES OF NUCLEIC ACIDS AT SURFACES RELEVANT TO MICROARRAY PERFORMANCE.

    Science.gov (United States)

    Rao, Archana N; Grainger, David W

    2014-04-01

    Both clinical and analytical metrics produced by microarray-based assay technology have recognized problems in reproducibility, reliability and analytical sensitivity. These issues are often attributed to poor understanding and control of nucleic acid behaviors and properties at solid-liquid interfaces. Nucleic acid hybridization, central to DNA and RNA microarray formats, depends on the properties and behaviors of single strand (ss) nucleic acids (e.g., probe oligomeric DNA) bound to surfaces. ssDNA's persistence length, radius of gyration, electrostatics, conformations on different surfaces and under various assay conditions, its chain flexibility and curvature, charging effects in ionic solutions, and fluorescent labeling all influence its physical chemistry and hybridization under assay conditions. Nucleic acid (e.g., both RNA and DNA) target interactions with immobilized ssDNA strands are highly impacted by these biophysical states. Furthermore, the kinetics, thermodynamics, and enthalpic and entropic contributions to DNA hybridization reflect global probe/target structures and interaction dynamics. Here we review several biophysical issues relevant to oligomeric nucleic acid molecular behaviors at surfaces and their influences on duplex formation that influence microarray assay performance. Correlation of biophysical aspects of single and double-stranded nucleic acids with their complexes in bulk solution is common. Such analysis at surfaces is not commonly reported, despite its importance to microarray assays. We seek to provide further insight into nucleic acid-surface challenges facing microarray diagnostic formats that have hindered their clinical adoption and compromise their research quality and value as genomics tools.

  10. BIOPHYSICAL PROPERTIES OF NUCLEIC ACIDS AT SURFACES RELEVANT TO MICROARRAY PERFORMANCE

    Science.gov (United States)

    Rao, Archana N.; Grainger, David W.

    2014-01-01

    Both clinical and analytical metrics produced by microarray-based assay technology have recognized problems in reproducibility, reliability and analytical sensitivity. These issues are often attributed to poor understanding and control of nucleic acid behaviors and properties at solid-liquid interfaces. Nucleic acid hybridization, central to DNA and RNA microarray formats, depends on the properties and behaviors of single strand (ss) nucleic acids (e.g., probe oligomeric DNA) bound to surfaces. ssDNA’s persistence length, radius of gyration, electrostatics, conformations on different surfaces and under various assay conditions, its chain flexibility and curvature, charging effects in ionic solutions, and fluorescent labeling all influence its physical chemistry and hybridization under assay conditions. Nucleic acid (e.g., both RNA and DNA) target interactions with immobilized ssDNA strands are highly impacted by these biophysical states. Furthermore, the kinetics, thermodynamics, and enthalpic and entropic contributions to DNA hybridization reflect global probe/target structures and interaction dynamics. Here we review several biophysical issues relevant to oligomeric nucleic acid molecular behaviors at surfaces and their influences on duplex formation that influence microarray assay performance. Correlation of biophysical aspects of single and double-stranded nucleic acids with their complexes in bulk solution is common. Such analysis at surfaces is not commonly reported, despite its importance to microarray assays. We seek to provide further insight into nucleic acid-surface challenges facing microarray diagnostic formats that have hindered their clinical adoption and compromise their research quality and value as genomics tools. PMID:24765522

  11. Biophysical Approach to Mechanisms of Cancer Prevention and Treatment with Green Tea Catechins.

    Science.gov (United States)

    Suganuma, Masami; Takahashi, Atsushi; Watanabe, Tatsuro; Iida, Keisuke; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Fujiki, Hirota

    2016-11-18

    Green tea catechin and green tea extract are now recognized as non-toxic cancer preventives for humans. We first review our brief historical development of green tea cancer prevention. Based on exciting evidence that green tea catechin, (-)-epigallocatechin gallate (EGCG) in drinking water inhibited lung metastasis of B16 melanoma cells, we and other researchers have studied the inhibitory mechanisms of metastasis with green tea catechins using biomechanical tools, atomic force microscopy (AFM) and microfluidic optical stretcher. Specifically, determination of biophysical properties of cancer cells, low cell stiffness, and high deformability in relation to migration, along with biophysical effects, were studied by treatment with green tea catechins. The study with AFM revealed that low average values of Young's moduli, indicating low cell stiffness, are closely associated with strong potential of cell migration and metastasis for various cancer cells. It is important to note that treatments with EGCG and green tea extract elevated the average values of Young's moduli resulting in increased stiffness (large elasticity) of melanomas and various cancer cells. We discuss here the biophysical basis of multifunctions of green tea catechins and green tea extract leading to beneficial effects for cancer prevention and treatment.

  12. Omega-3 Fatty Acids Modulate TRPV4 Function through Plasma Membrane Remodeling.

    Science.gov (United States)

    Caires, Rebeca; Sierra-Valdez, Francisco J; Millet, Jonathan R M; Herwig, Joshua D; Roan, Esra; Vásquez, Valeria; Cordero-Morales, Julio F

    2017-10-03

    Dietary consumption of ω-3 polyunsaturated fatty acids (PUFAs), present in fish oils, is known to improve the vascular response, but their molecular targets remain largely unknown. Activation of the TRPV4 channel has been implicated in endothelium-dependent vasorelaxation. Here, we studied the contribution of ω-3 PUFAs to TRPV4 function by precisely manipulating the fatty acid content in Caenorhabditis elegans. By genetically depriving the worms of PUFAs, we determined that the metabolism of ω-3 fatty acids is required for TRPV4 activity. Functional, lipid metabolome, and biophysical analyses demonstrated that ω-3 PUFAs enhance TRPV4 function in human endothelial cells and support the hypothesis that lipid metabolism and membrane remodeling regulate cell reactivity. We propose a model whereby the eicosanoid's epoxide group location increases membrane fluidity and influences the endothelial cell response by increasing TRPV4 channel activity. ω-3 PUFA-like molecules might be viable antihypertensive agents for targeting TRPV4 to reduce systemic blood pressure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Structural and biophysical characteristics of human skin in maintaining proper epidermal barrier function

    Directory of Open Access Journals (Sweden)

    Magdalena Boer

    2016-02-01

    Full Text Available The complex structure of human skin and its physicochemical properties turn it into an efficient outermost defence line against exogenous factors, and help maintain homeostasis of the human body. This role is played by the epidermal barrier with its major part – stratum corneum. The condition of the epidermal barrier depends on individual and environmental factors. The most important biophysical parameters characterizing the status of this barrier are the skin pH, epidermal hydration, transepidermal water loss and sebum excretion. The knowledge of biophysical skin processes may be useful for the implementation of prophylactic actions whose aim is to restore the barrier function.

  14. Nanoscale quantification of the biophysical characterization of combretastatin A-4-treated tumor cells using atomic force microscopy.

    Science.gov (United States)

    Li, Yanchun; Chen, Jv; Liu, Yutong; Zhang, Weige; He, Wenhui; Xu, Hanying; Liu, Lianqing; Ma, Enlong

    2017-01-01

    As an inhibitor of microtubule assembly, combretastatin A-4 (CA-4)-induced biological responses in tumor cells have been well known, but the corresponding changes in nano-biophysical properties were not investigated given the lack of an ideal tool. Using AFM technique, we investigated the alteration of nano-biophysical properties when CA-4-treated tumor cells underwent the different biological processes, including cell cycle arrest, apoptosis and autophagy. We found that CA-4-resistant cells were rougher with the presence of characteristic "ridges", indicating that the development of "ridge" structure may be a determinant of the sensitivity of cells to CA-4 compounds. CA-4 induced G2/M arrest and apoptosis in sensitive cells but triggered anti-apoptotic autophagy in resistant cells. CA-4 treatment caused an increase in stiffness in both sensitive and resistant cells. However, these cells exhibited different changes in cell surface roughness. CA-4 decreased Ra and Rq values in sensitive cells but increased these values in resistant cells. The reorganization of F-actin might contribute to the different changes of nano-biophysical properties in CA-4-sensitive and-resistant cells. Our results suggest that cellular nano-biophysical properties, such as "ridges", roughness and stiffness, could be applied as potential biomarkers for evaluating CA-4 compounds, and knowledge regarding how biological alterations cause changes in cellular nano-biophysical properties is helpful to develop a new high-resolution screening tool for anti-tumor agents.

  15. Biophysical approach to chronic kidney disease management in older patients

    Directory of Open Access Journals (Sweden)

    Alberto Foletti

    2016-06-01

    Full Text Available Chronic kidney disease (CKD and its clinical progression are a critical issue in an aging population. Therefore, strategies aimed at preventing and managing the decline of renal function are warranted. Recent evidence has provided encouraging results for the improvement of renal function achieved through an integrated biophysical approach, but prospective studies on the clinical efficacy of this strategy are still lacking. This was an open-label prospective pilot study to investigate the effect of electromagnetic information transfer through the aqueous system on kidney function of older patients affected by stage 1 or 2 CKD. Patients received biophysical therapy every 3 months over a 1-year period. Estimated glomerular filtration rate (eGFR values were calculated using the CKD–Epidemiology Collaboration formula, and were recorded at baseline and at the end of treatment. Overall, 58 patients (mean age 74.8 ± 3.7 years were included in the study. At baseline, mean eGFR was 64.6 ± 15.5 mL/min, and it significantly increased to 69.9 ± 15.8 mL/min after 1 year (+5.2 ± 10 mL/min, p<0.0002. The same trend was observed among men (+5.7 ± 10.2 mL/min, p<0.0064 and women (+4.7 ± 9.9 mL/min, p<0.014. When results were analyzed by sex, no difference was found between the 2 groups. Although further and larger prospective studies are needed, our findings suggest that an integrated biophysical approach may be feasible in the management of older patients with early-stage CKD, to reduce and prevent the decline of renal function due to aging or comorbidities.

  16. Photobiology of Symbiodinium revisited: bio-physical and bio-optical signatures

    Science.gov (United States)

    Hennige, S. J.; Suggett, D. J.; Warner, M. E.; McDougall, K. E.; Smith, D. J.

    2009-03-01

    Light is often the most abundant resource within the nutrient-poor waters surrounding coral reefs. Consequently, zooxanthellae ( Symbiodinium spp.) must continually photoacclimate to optimise productivity and ensure coral success. In situ coral photobiology is becoming dominated by routine assessments using state-of-the-art non-invasive bio-optical or chlorophyll a fluorescence (bio-physical) techniques. Multiple genetic types of Symbiodinium are now known to exist; however, little focus has been given as to how these types differ in terms of characteristics that are observable using these techniques. Therefore, this investigation aimed to revisit and expand upon a pivotal study by Iglesias-Prieto and Trench (1994) by comparing the photoacclimation characteristics of different Symbiodinium types based on their bio-physical (chlorophyll a fluorescence, reaction centre counts) and bio-optical (optical absorption, pigment concentrations) ‘signatures’. Signatures described here are unique to Symbiodinium type and describe phenotypic responses to set conditions, and hence are not suitable to describe taxonomic structure of in hospite Symbiodinium communities. In this study, eight Symbiodinium types from clades and sub-clades (A-B, F) were grown under two PFDs (Photon Flux Density) and examined. The photoacclimation response by Symbiodinium was highly variable between algal types for all bio-physical and for many bio-optical measurements; however, a general preference to modifying reaction centre content over effective antennae-absorption was observed. Certain bio-optically derived patterns, such as light absorption, were independent of algal type and, when considered per photosystem, were matched by reaction centre stoichiometry. Only by better understanding genotypic and phenotypic variability between Symbiodinium types can future studies account for the relative taxonomic and physiological contribution by Symbiodinium to coral acclimation.

  17. Biochemical enrichment and biophysical characterization of a taste receptor for L-arginine from the catfish, Ictalurus puntatus

    Directory of Open Access Journals (Sweden)

    Spielman Andrew I

    2004-07-01

    Full Text Available Abstract Background The channel catfish, Ictalurus punctatus, is invested with a high density of cutaneous taste receptors, particularly on the barbel appendages. Many of these receptors are sensitive to selected amino acids, one of these being a receptor for L-arginine (L-Arg. Previous neurophysiological and biophysical studies suggested that this taste receptor is coupled directly to a cation channel and behaves as a ligand-gated ion channel receptor (LGICR. Earlier studies demonstrated that two lectins, Ricinus communis agglutinin I (RCA-I and Phaseolus vulgaris Erythroagglutinin (PHA-E, inhibited the binding of L-Arg to its presumed receptor sites, and that PHA-E inhibited the L-Arg-stimulated ion conductance of barbel membranes reconstituted into lipid bilayers. Results Both PHA-E and RCA-I almost exclusively labeled an 82–84 kDa protein band of an SDS-PAGE of solubilized barbel taste epithelial membranes. Further, both rhodamine-conjugated RCA-I and polyclonal antibodies raised to the 82–84 kDa electroeluted peptides labeled the apical region of catfish taste buds. Because of the specificity shown by RCA-I, lectin affinity was chosen as the first of a three-step procedure designed to enrich the presumed LGICR for L-Arg. Purified and CHAPS-solubilized taste epithelial membrane proteins were subjected successively to (1, lectin (RCA-I affinity; (2, gel filtration (Sephacryl S-300HR; and (3, ion exchange chromatography. All fractions from each chromatography step were evaluated for L-Arg-induced ion channel activity by reconstituting each fraction into a lipid bilayer. Active fractions demonstrated L-Arg-induced channel activity that was inhibited by D-arginine (D-Arg with kinetics nearly identical to those reported earlier for L-Arg-stimulated ion channels of native barbel membranes reconstituted into lipid bilayers. After the final enrichment step, SDS-PAGE of the active ion channel protein fraction revealed a single band at 82–84 k

  18. Progress and challenges of engineering a biophysical CO2-concentrating mechanism into higher plants.

    Science.gov (United States)

    Rae, Benjamin D; Long, Benedict M; Förster, Britta; Nguyen, Nghiem D; Velanis, Christos N; Atkinson, Nicky; Hee, Wei Yih; Mukherjee, Bratati; Price, G Dean; McCormick, Alistair J

    2017-06-01

    Growth and productivity in important crop plants is limited by the inefficiencies of the C3 photosynthetic pathway. Introducing CO2-concentrating mechanisms (CCMs) into C3 plants could overcome these limitations and lead to increased yields. Many unicellular microautotrophs, such as cyanobacteria and green algae, possess highly efficient biophysical CCMs that increase CO2 concentrations around the primary carboxylase enzyme, Rubisco, to enhance CO2 assimilation rates. Algal and cyanobacterial CCMs utilize distinct molecular components, but share several functional commonalities. Here we outline the recent progress and current challenges of engineering biophysical CCMs into C3 plants. We review the predicted requirements for a functional biophysical CCM based on current knowledge of cyanobacterial and algal CCMs, the molecular engineering tools and research pipelines required to translate our theoretical knowledge into practice, and the current challenges to achieving these goals. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Biophysical characterization of the proton-coupled oligopeptide transporter YjdL

    DEFF Research Database (Denmark)

    Jensen, Johanne Mørch; Simonsen, Fie C.; Mastali, Amir

    2012-01-01

    significantly different from prototypical POTs such as the human hPepT1. Nonetheless YjdL contains several highly conserved POT residues, which include Glu388 that is located in the putative substrate binding cavity. Here we present biophysical characterization of WT-YjdL and Glu388Gln. Isothermal titration...

  20. Staphylococcal phenotypes induced by naturally occurring and synthetic membrane-interactive polyphenolic β-lactam resistance modifiers.

    Directory of Open Access Journals (Sweden)

    Lucia Palacios

    Full Text Available Galloyl catechins, in particular (--epicatechin gallate (ECg, have the capacity to abrogate β-lactam resistance in methicillin-resistant strains of Staphylococcus aureus (MRSA; they also prevent biofilm formation, reduce the secretion of a large proportion of the exoproteome and induce profound changes to cell morphology. Current evidence suggests that these reversible phenotypic traits result from their intercalation into the bacterial cytoplasmic membrane. We have endeavoured to potentiate the capacity of ECg to modify the MRSA phenotype by stepwise removal of hydroxyl groups from the B-ring pharmacophore and the A:C fused ring system of the naturally occurring molecule. ECg binds rapidly to the membrane, inducing up-regulation of genes responsible for protection against cell wall stress and maintenance of membrane integrity and function. Studies with artificial membranes modelled on the lipid composition of the staphylococcal bilayer indicated that ECg adopts a position deep within the lipid palisade, eliciting major alterations in the thermotropic behaviour of the bilayer. The non-galloylated homolog (--epicatechin enhanced ECg-mediated effects by facilitating entry of ECg molecules into the membrane. ECg analogs with unnatural B-ring hydroxylation patterns induced higher levels of gene expression and more profound changes to MRSA membrane fluidity than ECg but adopted a more superficial location within the bilayer. ECg possessed a high affinity for the positively charged staphylococcal membrane and induced changes to the biophysical properties of the bilayer that are likely to account for its capacity to disperse the cell wall biosynthetic machinery responsible for β-lactam resistance. The ability to enhance these properties by chemical modification of ECg raises the possibility that more potent analogs could be developed for clinical evaluation.

  1. The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part I: cellular response.

    Science.gov (United States)

    Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

    2015-02-01

    Osteoarthritis (OA) is a complex disease of the joint for which current treatments are unsatisfactory, thus motivating development of tissue engineering (TE)-based therapies. To date, TE strategies have had some success, developing replacement tissue constructs with biochemical properties approaching that of native cartilage. However, poor biomechanical properties and limited postimplantation integration with surrounding tissue are major shortcomings that need to be addressed. Functional tissue engineering strategies that apply physiologically relevant biophysical cues provide a platform to improve TE constructs before implantation. In the previous decade, new experimental and theoretical findings in cartilage biomechanics and electromechanics have emerged, resulting in an increased understanding of the complex interplay of multiple biophysical cues in the extracellular matrix of the tissue. The effect of biophysical stimulation on cartilage, and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair, has, therefore, been extensively explored by the TE community. This article compares and contrasts the cellular response of chondrocytes to multiple biophysical stimuli, and may be read in conjunction with its companion paper that compares and contrasts the subsequent intracellular signal transduction cascades. Mechanical, magnetic, and electrical stimuli promote proliferation, differentiation, and maturation of chondrocytes within established dose parameters or "biological windows." This knowledge will provide a framework for ongoing studies incorporating multiple biophysical cues in TE functional neocartilage for treatment of OA.

  2. The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part II: signal transduction.

    Science.gov (United States)

    Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

    2015-02-01

    The unique mechanoelectrochemical environment of cartilage has motivated researchers to investigate the effect of multiple biophysical cues, including mechanical, magnetic, and electrical stimulation, on chondrocyte biology. It is well established that biophysical stimuli promote chondrocyte proliferation, differentiation, and maturation within "biological windows" of defined dose parameters, including mode, frequency, magnitude, and duration of stimuli (see companion review Part I: Cellular Response). However, the underlying molecular mechanisms and signal transduction pathways activated in response to multiple biophysical stimuli remain to be elucidated. Understanding the mechanisms of biophysical signal transduction will deepen knowledge of tissue organogenesis, remodeling, and regeneration and aiding in the treatment of pathologies such as osteoarthritis. Further, this knowledge will provide the tissue engineer with a potent toolset to manipulate and control cell fate and subsequently develop functional replacement cartilage. The aim of this article is to review chondrocyte signal transduction pathways in response to mechanical, magnetic, and electrical cues. Signal transduction does not occur along a single pathway; rather a number of parallel pathways appear to be activated, with calcium signaling apparently common to all three types of stimuli, though there are different modes of activation. Current tissue engineering strategies, such as the development of "smart" functionalized biomaterials that enable the delivery of growth factors or integration of conjugated nanoparticles, may further benefit from targeting known signal transduction pathways in combination with external biophysical cues.

  3. Predictive biophysical modeling and understanding of the dynamics of mRNA translation and its evolution

    Science.gov (United States)

    Zur, Hadas; Tuller, Tamir

    2016-01-01

    mRNA translation is the fundamental process of decoding the information encoded in mRNA molecules by the ribosome for the synthesis of proteins. The centrality of this process in various biomedical disciplines such as cell biology, evolution and biotechnology, encouraged the development of dozens of mathematical and computational models of translation in recent years. These models aimed at capturing various biophysical aspects of the process. The objective of this review is to survey these models, focusing on those based and/or validated on real large-scale genomic data. We consider aspects such as the complexity of the models, the biophysical aspects they regard and the predictions they may provide. Furthermore, we survey the central systems biology discoveries reported on their basis. This review demonstrates the fundamental advantages of employing computational biophysical translation models in general, and discusses the relative advantages of the different approaches and the challenges in the field. PMID:27591251

  4. Lipid chain saturation and the cholesterol in the phospholipid membrane affect the spectroscopic properties of lipophilic dye nile red

    Science.gov (United States)

    Halder, Animesh; Saha, Baishakhi; Maity, Pabitra; Kumar, Gopinatha Suresh; Sinha, Deepak Kumar; Karmakar, Sanat

    2018-02-01

    We have studied the effect of composition and the phase state of phospholipid membranes on the emission spectrum, anisotropy and lifetime of a lipophilic fluorescence probe nile red. Fluorescence spectrum of nile red in membranes containing cholesterol has also been investigated in order to get insights into the influence of cholesterol on the phospholipid membranes. Maximum emission wavelength (λem) of nile red in the fluid phase of saturated and unsaturated phospholipids was found to differ by 10 nm. The λem was also found to be independent of chain length and charge of the membrane. However, the λem is strongly dependent on the temperature in the gel phase. The λem and rotational diffusion rate decrease, whereas the anisotropy and lifetime increase markedly with increasing cholesterol concentration for saturated phosoholipids, such as, dimyristoyl phosphatidylcholine (DMPC) in the liquid ordered phase. However, these spectroscopic properties do not alter significantly in case of unsaturated phospholipids, such as, dioleoyl phosphatidylcholine (DOPC) in liquid disordered phase. Interestingly, red edge excitation shift (REES) in the presence of lipid-cholesterol membranes is the direct consequences of change in rotational diffusion due to motional restriction of lipids in the presence of cholesterol. This study provides correlations between the membrane compositions and fluorescence spectral features which can be utilized in a wide range of biophysical fields as well the cell biology.

  5. The cytotoxic activity of miltefosine against Leishmania and macrophages is associated with dynamic changes in plasma membrane proteins.

    Science.gov (United States)

    Fernandes, Kelly Souza; de Souza, Paulo Eduardo Narcizo; Dorta, Miriam Leandro; Alonso, Antonio

    2017-01-01

    In this study, we combined electron paramagnetic resonance (EPR) spectroscopy with an analysis of biophysical cellular parameters to study the mechanisms underlying the in vitro anti-leishmanial activity of miltefosine (MT). A thiol-specific spin label attached to membrane-bound proteins of Leishmania amazonensis and peritoneal macrophages indicated that MT may bind to plasma membrane proteins in large quantities via a detergent-like action and cause structural changes associated with a marked increase in dynamics and exposure to an aqueous environment. EPR spectra of a spin-labeled stearic acid indicated strong interactions between the probe and membrane proteins and a marked increase in the membrane fluidity of MT-treated cells. The cytotoxicity of MT was found to depend on the cell concentration used in the assay. This dependence was described by an equation involving the 50% inhibitory concentrations of MT in the aqueous medium (c w50 ) and the cell membrane (c m50 ) and the membrane-aqueous medium partition coefficient of MT (K). With a c w50 of 8.7μM, macrophages were less sensitive to MT than amastigotes and promastigotes of Leishmania, which had c w50 values of 2.4-3.1μM. The estimated c m50 of MT for Leishmania was 1.8M, which appears sufficient to cause ruptures or formation of pores in the plasma membrane. Additionally, we demonstrated that the changes in the plasma membrane detected by EPR spectroscopy occurred at cytotoxic concentrations of MT, as assessed through in vitro assays. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Biophysical and sociocultural factors underlying spatial trade-offs of ecosystem services in semiarid watersheds

    Directory of Open Access Journals (Sweden)

    Marina García-Llorente

    2015-09-01

    Full Text Available Biophysical and social systems are linked to form social-ecological systems whose sustainability depends on their capacity to absorb uncertainty and cope with disturbances. In this study, we explored the key biophysical and socio-cultural factors underlying ecosystem service supply in two semiarid watersheds of southern Spain. These included variables associated with the role that freshwater flows and biodiversity play in securing the system's capacity to sustain essential ecosystem services and their relationship with social demand for services, local water governance, and land-use intensification. Our results reveal the importance of considering the invisible dimensions of water and biodiversity, i.e. green freshwater flows and trait-based indicators, because of their relevance to the supply of ecosystem services. Furthermore, they uncover the importance of traditional irrigation canals, a local water governance system, in maintaining the ecosystems' capacity to supply services. The study also highlights the complex trade-offs that occur because of the spatial mismatch between ecosystem service supply (upstream and ecosystem service demand (downstream in watersheds. Finally, we found that land-use intensification generally resulted in losses of the biophysical factors that underpin the supply of some ecosystem services, increases in social demand for less diversified services, and the abandonment of local governance practices. Attempts to manage social-ecological systems toward sustainability at the local scale should identify the key biophysical and socio-cultural factors that are essential for maintaining ecosystem services and should recognize existing interrelationships between them. Land-use management should also take into account ecosystem service trade-offs and the consequences resulting from land-use intensification.

  7. LBA-ECO ND-01 Reflectance and Biophysical Measures, Grass Pastures: Rondonia, Brazil

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: This data set provides the results of spectral reflectance (350 to 2,500 nm at 1-nm increments) and biophysical measurements on grass pastures in eight...

  8. Estimation efficiency of usage satellite derived and modelled biophysical products for yield forecasting

    Science.gov (United States)

    Kolotii, Andrii; Kussul, Nataliia; Skakun, Sergii; Shelestov, Andrii; Ostapenko, Vadim; Oliinyk, Tamara

    2015-04-01

    Efficient and timely crop monitoring and yield forecasting are important tasks for ensuring of stability and sustainable economic development [1]. As winter crops pay prominent role in agriculture of Ukraine - the main focus of this study is concentrated on winter wheat. In our previous research [2, 3] it was shown that usage of biophysical parameters of crops such as FAPAR (derived from Geoland-2 portal as for SPOT Vegetation data) is far more efficient for crop yield forecasting to NDVI derived from MODIS data - for available data. In our current work efficiency of usage such biophysical parameters as LAI, FAPAR, FCOVER (derived from SPOT Vegetation and PROBA-V data at resolution of 1 km and simulated within WOFOST model) and NDVI product (derived from MODIS) for winter wheat monitoring and yield forecasting is estimated. As the part of crop monitoring workflow (vegetation anomaly detection, vegetation indexes and products analysis) and yield forecasting SPIRITS tool developed by JRC is used. Statistics extraction is done for landcover maps created in SRI within FP-7 SIGMA project. Efficiency of usage satellite based and modelled with WOFOST model biophysical products is estimated. [1] N. Kussul, S. Skakun, A. Shelestov, O. Kussul, "Sensor Web approach to Flood Monitoring and Risk Assessment", in: IGARSS 2013, 21-26 July 2013, Melbourne, Australia, pp. 815-818. [2] F. Kogan, N. Kussul, T. Adamenko, S. Skakun, O. Kravchenko, O. Kryvobok, A. Shelestov, A. Kolotii, O. Kussul, and A. Lavrenyuk, "Winter wheat yield forecasting in Ukraine based on Earth observation, meteorological data and biophysical models," International Journal of Applied Earth Observation and Geoinformation, vol. 23, pp. 192-203, 2013. [3] Kussul O., Kussul N., Skakun S., Kravchenko O., Shelestov A., Kolotii A, "Assessment of relative efficiency of using MODIS data to winter wheat yield forecasting in Ukraine", in: IGARSS 2013, 21-26 July 2013, Melbourne, Australia, pp. 3235 - 3238.

  9. Membrane Stored Curvature Elastic Stress Modulates Recruitment of Maintenance Proteins PspA and Vipp1.

    Science.gov (United States)

    McDonald, Christopher; Jovanovic, Goran; Ces, Oscar; Buck, Martin

    2015-09-01

    Phage shock protein A (PspA), which is responsible for maintaining inner membrane integrity under stress in enterobacteria, and vesicle-inducting protein in plastids 1 (Vipp1), which functions for membrane maintenance and thylakoid biogenesis in cyanobacteria and plants, are similar peripheral membrane-binding proteins. Their homologous N-terminal amphipathic helices are required for membrane binding; however, the membrane features recognized and required for expressing their functionalities have remained largely uncharacterized. Rigorously controlled, in vitro methodologies with lipid vesicles and purified proteins were used in this study and provided the first biochemical and biophysical characterizations of membrane binding by PspA and Vipp1. Both proteins are found to sense stored curvature elastic (SCE) stress and anionic lipids within the membrane. PspA has an enhanced sensitivity for SCE stress and a higher affinity for the membrane than Vipp1. These variations in binding may be crucial for some of the proteins' differing roles in vivo. Assays probing the transcriptional regulatory function of PspA in the presence of vesicles showed that a relief of transcription inhibition occurs in an SCE stress-specific manner. This in vitro recapitulation of membrane stress-dependent transcription control suggests that the Psp response may be mounted in vivo when a cell's inner membrane experiences increased SCE stress. All cell types maintain the integrity of their membrane systems. One widely distributed membrane stress response system in bacteria is the phage shock protein (Psp) system. The central component, peripheral membrane protein PspA, which mitigates inner membrane stress in bacteria, has a counterpart, Vipp1, which functions for membrane maintenance and thylakoid biogenesis in plants and photosynthetic bacteria. Membrane association of both these proteins is accepted as playing a pivotal role in their functions. Here we show that direct membrane binding by

  10. Low temperature experiments in radiation biophysics

    International Nuclear Information System (INIS)

    Moan, J.

    1977-01-01

    The reasons for performing experiments in radiation biophysics at low temperatures, whereby electron spectra may be studied, are explained. The phenomenon of phosphorescence spectra observed in frozen aqueous solutions of tryptophan and adenosine is also described. Free radicals play an important part in biological radiation effects and may be studied by ESR spectroscopy. An ESR spectrum of T 1 bacteriophages irradiated dry at 130K is illustrated and discussed. Hydrogen atoms, which give lines on the spectrum, are believed to be those radiation products causing most biological damage in a dry system. Low temperature experiments are of great help in explaining the significance of direct and indirect effects. This is illustrated for the case of trypsin. (JIW)

  11. Biophysical basis for the geometry of conical stromatolites.

    Science.gov (United States)

    Petroff, Alexander P; Sim, Min Sub; Maslov, Andrey; Krupenin, Mikhail; Rothman, Daniel H; Bosak, Tanja

    2010-06-01

    Stromatolites may be Earth's oldest macroscopic fossils; however, it remains controversial what, if any, biological processes are recorded in their morphology. Although the biological interpretation of many stromatolite morphologies is confounded by the influence of sedimentation, conical stromatolites form in the absence of sedimentation and are, therefore, considered to be the most robust records of biophysical processes. A qualitative similarity between conical stromatolites and some modern microbial mats suggests a photosynthetic origin for ancient stromatolites. To better understand and interpret ancient fossils, we seek a quantitative relationship between the geometry of conical stromatolites and the biophysical processes that control their growth. We note that all modern conical stromatolites and many that formed in the last 2.8 billion years display a characteristic centimeter-scale spacing between neighboring structures. To understand this prominent-but hitherto uninterpreted-organization, we consider the role of diffusion in mediating competition between stromatolites. Having confirmed this model through laboratory experiments and field observation, we find that organization of a field of stromatolites is set by a diffusive time scale over which individual structures compete for nutrients, thus linking form to physiology. The centimeter-scale spacing between modern and ancient stromatolites corresponds to a rhythmically fluctuating metabolism with a period of approximately 20 hr. The correspondence between the observed spacing and the day length provides quantitative support for the photosynthetic origin of conical stromatolites throughout geologic time.

  12. Biophysics of filament length regulation by molecular motors

    International Nuclear Information System (INIS)

    Kuan, Hui-Shun; Betterton, M D

    2013-01-01

    Regulating physical size is an essential problem that biological organisms must solve from the subcellular to the organismal scales, but it is not well understood what physical principles and mechanisms organisms use to sense and regulate their size. Any biophysical size-regulation scheme operates in a noisy environment and must be robust to other cellular dynamics and fluctuations. This work develops theory of filament length regulation inspired by recent experiments on kinesin-8 motor proteins, which move with directional bias on microtubule filaments and alter microtubule dynamics. Purified kinesin-8 motors can depolymerize chemically-stabilized microtubules. In the length-dependent depolymerization model, the rate of depolymerization tends to increase with filament length, because long filaments accumulate more motors at their tips and therefore shorten more quickly. When balanced with a constant filament growth rate, this mechanism can lead to a fixed polymer length. However, the mechanism by which kinesin-8 motors affect the length of dynamic microtubules in cells is less clear. We study the more biologically realistic problem of microtubule dynamic instability modulated by a motor-dependent increase in the filament catastrophe frequency. This leads to a significant decrease in the mean filament length and a narrowing of the filament length distribution. The results improve our understanding of the biophysics of length regulation in cells. (paper)

  13. Planar Optical Nanoantennas Resolve Cholesterol-Dependent Nanoscale Heterogeneities in the Plasma Membrane of Living Cells

    Science.gov (United States)

    Regmi, Raju; Winkler, Pamina M.; Flauraud, Valentin; Borgman, Kyra J. E.; Manzo, Carlo; Brugger, Jürgen; Rigneault, Hervé; Wenger, Jérôme; García-Parajo, María F.

    2017-10-01

    Optical nanoantennas can efficiently confine light into nanoscopic hotspots, enabling single-molecule detection sensitivity at biological relevant conditions. This innovative approach to breach the diffraction limit offers a versatile platform to investigate the dynamics of individual biomolecules in living cell membranes and their partitioning into cholesterol-dependent lipid nanodomains. Here, we present optical nanoantenna arrays with accessible surface hotspots to study the characteristic diffusion dynamics of phosphoethanolamine (PE) and sphingomyelin (SM) in the plasma membrane of living cells at the nanoscale. Fluorescence burst analysis and fluorescence correlation spectroscopy performed on nanoantennas of different gap sizes show that, unlike PE, SM is transiently trapped in cholesterol-enriched nanodomains of 10 nm diameter with short characteristic times around 100 {\\mu}s. The removal of cholesterol led to the free diffusion of SM, consistent with the dispersion of nanodomains. Our results are consistent with the existence of highly transient and fluctuating nanoscale assemblies enriched by cholesterol and sphingolipids in living cell membranes, also known as lipid rafts. Quantitative data on sphingolipids partitioning into lipid rafts is crucial to understand the spatiotemporal heterogeneous organization of transient molecular complexes on the membrane of living cells at the nanoscale. The proposed technique is fully biocompatible and thus provides various opportunities for biophysics and live cell research to reveal details that remain hidden in confocal diffraction-limited measurements.

  14. Biophysical Approach to Mechanisms of Cancer Prevention and Treatment with Green Tea Catechins

    Directory of Open Access Journals (Sweden)

    Masami Suganuma

    2016-11-01

    Full Text Available Green tea catechin and green tea extract are now recognized as non-toxic cancer preventives for humans. We first review our brief historical development of green tea cancer prevention. Based on exciting evidence that green tea catechin, (−-epigallocatechin gallate (EGCG in drinking water inhibited lung metastasis of B16 melanoma cells, we and other researchers have studied the inhibitory mechanisms of metastasis with green tea catechins using biomechanical tools, atomic force microscopy (AFM and microfluidic optical stretcher. Specifically, determination of biophysical properties of cancer cells, low cell stiffness, and high deformability in relation to migration, along with biophysical effects, were studied by treatment with green tea catechins. The study with AFM revealed that low average values of Young’s moduli, indicating low cell stiffness, are closely associated with strong potential of cell migration and metastasis for various cancer cells. It is important to note that treatments with EGCG and green tea extract elevated the average values of Young’s moduli resulting in increased stiffness (large elasticity of melanomas and various cancer cells. We discuss here the biophysical basis of multifunctions of green tea catechins and green tea extract leading to beneficial effects for cancer prevention and treatment.

  15. Variation of Biophysical Parameters of the Skin with Age, Gender, and Body Region

    Science.gov (United States)

    Firooz, Alireza; Sadr, Bardia; Babakoohi, Shahab; Sarraf-Yazdy, Maryam; Fanian, Ferial; Kazerouni-Timsar, Ali; Nassiri-Kashani, Mansour; Naghizadeh, Mohammad Mehdi; Dowlati, Yahya

    2012-01-01

    Background. Understanding the physiological, chemical, and biophysical characteristics of the skin helps us to arrange a proper approach to the management of skin diseases. Objective. The aim of this study was to measure 6 biophysical characteristics of normal skin (sebum content, hydration, transepidermal water loss (TEWL), erythema index, melanin index, and elasticity) in a normal population and assess the effect of sex, age, and body location on them. Methods. Fifty healthy volunteers in 5 age groups (5 males and females in each) were enrolled in this study. A multifunctional skin physiology monitor (Courage & Khazaka electronic GmbH, Germany) was used to measure skin sebum content, hydration, TEWL, erythema index, melanin index, and elasticity in 8 different locations of the body. Results. There were significant differences between the hydration, melanin index, and elasticity of different age groups. Regarding the locations, forehead had the highest melanin index, where as palm had the lowest value. The mean values of erythema index and melanin index and TEWL were significantly higher in males and anatomic location was a significant independent factor for all of 6 measured parameters. Conclusion. Several biophysical properties of the skin vary among different gender, age groups, and body locations. PMID:22536139

  16. The Instrumentation of a Microfluidic Analyzer Enabling the Characterization of the Specific Membrane Capacitance, Cytoplasm Conductivity, and Instantaneous Young's Modulus of Single Cells.

    Science.gov (United States)

    Wang, Ke; Zhao, Yang; Chen, Deyong; Huang, Chengjun; Fan, Beiyuan; Long, Rong; Hsieh, Chia-Hsun; Wang, Junbo; Wu, Min-Hsien; Chen, Jian

    2017-06-19

    This paper presents the instrumentation of a microfluidic analyzer enabling the characterization of single-cell biophysical properties, which includes seven key components: a microfluidic module, a pressure module, an imaging module, an impedance module, two LabVIEW platforms for instrument operation and raw data processing, respectively, and a Python code for data translation. Under the control of the LabVIEW platform for instrument operation, the pressure module flushes single cells into the microfluidic module with raw biophysical parameters sampled by the imaging and impedance modules and processed by the LabVIEW platform for raw data processing, which were further translated into intrinsic cellular biophysical parameters using the code developed in Python. Based on this system, specific membrane capacitance, cytoplasm conductivity, and instantaneous Young's modulus of three cell types were quantified as 2.76 ± 0.57 μF/cm², 1.00 ± 0.14 S/m, and 3.79 ± 1.11 kPa for A549 cells ( n cell = 202); 1.88 ± 0.31 μF/cm², 1.05 ± 0.16 S/m, and 3.74 ± 0.75 kPa for 95D cells ( n cell = 257); 2.11 ± 0.38 μF/cm², 0.87 ± 0.11 S/m, and 5.39 ± 0.89 kPa for H460 cells ( n cell = 246). As a semi-automatic instrument with a throughput of roughly 1 cell per second, this prototype instrument can be potentially used for the characterization of cellular biophysical properties.

  17. High anisotropy of flow-aligned bicellar membrane systems

    KAUST Repository

    Kogan, Maxim

    2013-10-01

    In recent years, multi-lipid bicellar systems have emerged as promising membrane models. The fast orientational diffusion and magnetic alignability made these systems very attractive for NMR investigations. However, their alignment was so far achieved with a strong magnetic field, which limited their use with other methods that require macroscopic orientation. Recently, it was shown that bicelles could be aligned also by shear flow in a Couette flow cell, making it applicable to structural and biophysical studies by polarized light spectroscopy. Considering the sensitivity of this lipid system to small variations in composition and physicochemical parameters, efficient use of such a flow-cell method with coupled techniques will critically depend on the detailed understanding of how the lipid systems behave under flow conditions. In the present study we have characterized the flow alignment behavior of the commonly used dimyristoyl phosphatidylcholine/dicaproyl phosphatidylcholine (DMPC/DHPC) bicelle system, for various temperatures, lipid compositions, and lipid concentrations. We conclude that at optimal flow conditions the selected bicellar systems can produce the most efficient flow alignment out of any lipid systems used so far. The highest degree of orientation of DMPC/DHPC samples is noticed in a narrow temperature interval, at a practical temperature around 25 C, most likely in the phase transition region characterized by maximum sample viscosity. The change of macroscopic orientation factor as function of the above conditions is now described in detail. The increase in macroscopic alignment observed for bicelles will most likely allow recording of higher resolution spectra on membrane systems, which provide deeper structural insight and analysis into properties of biomolecules interacting with solution phase lipid membranes. © 2013 Elsevier Ireland Ltd.

  18. The Biophysics Microgravity Initiative

    Science.gov (United States)

    Gorti, S.

    2016-01-01

    Biophysical microgravity research on the International Space Station using biological materials has been ongoing for several decades. The well-documented substantive effects of long duration microgravity include the facilitation of the assembly of biological macromolecules into large structures, e.g., formation of large protein crystals under micro-gravity. NASA is invested not only in understanding the possible physical mechanisms of crystal growth, but also promoting two flight investigations to determine the influence of µ-gravity on protein crystal quality. In addition to crystal growth, flight investigations to determine the effects of shear on nucleation and subsequent formation of complex structures (e.g., crystals, fibrils, etc.) are also supported. It is now considered that long duration microgravity research aboard the ISS could also make possible the formation of large complex biological and biomimetic materials. Investigations of various materials undergoing complex structure formation in microgravity will not only strengthen NASA science programs, but may also provide invaluable insight towards the construction of large complex tissues, organs, or biomimetic materials on Earth.

  19. Predicting the Presence of Scyphozoan Jellyfish in the Gulf of Mexico Using a Biophysical Model

    Science.gov (United States)

    Aleksa, K. T.; Nero, R. W.; Wiggert, J. D.; Graham, W. M.

    2016-02-01

    The study and quantification of jellyfish (cnidarian medusae and ctenophores) is difficult due to their fragile body plan and a composition similar to their environment. The development of a predictive biophysical jellyfish model would be the first of its kind for the Gulf of Mexico and could provide assistance in ecological research and human interactions. In this study, the collection data of two scyphozoan medusae, Chrysaora quinquecirrha and Aurelia spp., were extracted from SEAMAP trawling surveys and were used to determine biophysical predictors for the presence of large jellyfish medusae in the Gulf of Mexico. Both in situ and remote sensing measurements from 2003 to 2013 were obtained. Logistic regressions were then applied to 27 biophysical parameters derived from these data to explore and determine significant predictors for the presence of medusae. Significant predictors identified by this analysis included water temperature, chlorophyll a, turbidity, distance from shore, and salinity. Future application for this model include foraging assessment of gelatinous predators as well as possible near real time monitoring of the distribution and movement of these medusae in the Gulf of Mexico.

  20. Human Pluripotent Stem Cell Mechanobiology: Manipulating the Biophysical Microenvironment for Regenerative Medicine and Tissue Engineering Applications.

    Science.gov (United States)

    Ireland, Ronald G; Simmons, Craig A

    2015-11-01

    A stem cell in its microenvironment is subjected to a myriad of soluble chemical cues and mechanical forces that act in concert to orchestrate cell fate. Intuitively, many of these soluble and biophysical factors have been the focus of intense study to successfully influence and direct cell differentiation in vitro. Human pluripotent stem cells (hPSCs) have been of considerable interest in these studies due to their great promise for regenerative medicine. Culturing and directing differentiation of hPSCs, however, is currently extremely labor-intensive and lacks the efficiency required to generate large populations of clinical-grade cells. Improved efficiency may come from efforts to understand how the cell biophysical signals can complement biochemical signals to regulate cell pluripotency and direct differentiation. In this concise review, we explore hPSC mechanobiology and how the hPSC biophysical microenvironment can be manipulated to maintain and differentiate hPSCs into functional cell types for regenerative medicine and tissue engineering applications. © 2015 AlphaMed Press.

  1. Two-Phase Contiguous Supported Lipid Bilayer Model for Membrane Rafts via Polymer Blotting and Stenciling.

    Science.gov (United States)

    Richards, Mark J; Daniel, Susan

    2017-02-07

    The supported lipid bilayer has been portrayed as a useful model of the cell membrane compatible with many biophysical tools and techniques that demonstrate its appeal in learning about the basic features of the plasma membrane. However, some of its potential has yet to be realized, particularly in the area of bilayer patterning and phase/composition heterogeneity. In this work, we generate contiguous bilayer patterns as a model system that captures the general features of membrane domains and lipid rafts. Micropatterned polymer templates of two types are investigated for generating patterned bilayer formation: polymer blotting and polymer lift-off stenciling. While these approaches have been used previously to create bilayer arrays by corralling bilayers patches with various types of boundaries impenetrable to bilayer diffusion, unique to the methods presented here, there are no physical barriers to diffusion. In this work, interfaces between contiguous lipid phases define the pattern shapes, with continuity between them allowing transfer of membrane-bound biomolecules between the phases. We examine effectors of membrane domain stability including temperature and cholesterol content to investigate domain dynamics. Contiguous patterning of supported bilayers as a model of lipid rafts expands the application of the SLB to an area with current appeal and brings with it a useful toolset for characterization and analysis. These combined tools should be helpful to researchers investigating lipid raft dynamics and function and biomolecule partitioning studies. Additionally, this patterning technique may be useful for applications such as bioseparations that exploit differences in lipid phase partitioning or creation of membranes that bind species like viruses preferentially at lipid phase boundaries, to name a few.

  2. Riparian influences on the biophysical characteristics of seston in headwater streams.

    Science.gov (United States)

    Scott R. Elliott; Robert J. Naiman; Peter A. Bisson

    2004-01-01

    Suspended particles (seston) in streams are an important source of nutrition for many invertebrates, forming a strong trophic link between plant and animal production. In forested regions the management of riparian corridors may alter alloehthonous and autochthonous contributions to streams, ultimately changing the biophysical characteristics of seston. This article...

  3. Biophysical studies of irradiated thymocytes. 1. Surface changes

    Energy Technology Data Exchange (ETDEWEB)

    Sungurov, A Yu; Tokalov, S V; Petrov, Yu P; Sharlaeva, T M

    1985-08-15

    In order to study postirradiation changes in thymus lymphocyte surface, a number of biophysical analytical methods was used: the cell two-partition method, the physical adhesion method, fluorescence intensity and binding parameters of negatively charged ANS probe. Reduction of cell distribution factor in two-phase system and adhesion of thymocytes to cotton 1 hour after irradiation, as well as abrupt change in parameters of binding the probe in the interval of 3-4 hours after X-ray irradiation at the dose of 4 Gy are demonstrated.

  4. Effect of therapeutic concentration of lithium on live HEK293 cells, increase of Na+/K+-ATPase, change of overall protein composition and alteration of surface layer of plasma membrane

    Czech Academy of Sciences Publication Activity Database

    Vošahlíková, Miroslava; Ujčíková, Hana; Chernyavskiy, Oleksandr; Brejchová, Jana; Roubalová, Lenka; Alda, M.; Svoboda, Petr

    2017-01-01

    Roč. 1861, č. 5 (2017), s. 1099-1112 ISSN 0304-4165 R&D Projects: GA ČR(CZ) GAP207/12/0919; GA ČR(CZ) GA15-16605S; GA ČR(CZ) GA17-07070S Institutional support: RVO:67985823 Keywords : lithium * HEK293 cells * Na+/K+-ATPase * membrane biophysics * proteomic analysis Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 4.702, year: 2016

  5. Similar Biophysical Abnormalities in Glomeruli and Podocytes from Two Distinct Models.

    Science.gov (United States)

    Embry, Addie E; Liu, Zhenan; Henderson, Joel M; Byfield, F Jefferson; Liu, Liping; Yoon, Joonho; Wu, Zhenzhen; Cruz, Katrina; Moradi, Sara; Gillombardo, C Barton; Hussain, Rihanna Z; Doelger, Richard; Stuve, Olaf; Chang, Audrey N; Janmey, Paul A; Bruggeman, Leslie A; Miller, R Tyler

    2018-03-23

    Background FSGS is a pattern of podocyte injury that leads to loss of glomerular function. Podocytes support other podocytes and glomerular capillary structure, oppose hemodynamic forces, form the slit diaphragm, and have mechanical properties that permit these functions. However, the biophysical characteristics of glomeruli and podocytes in disease remain unclear. Methods Using microindentation, atomic force microscopy, immunofluorescence microscopy, quantitative RT-PCR, and a three-dimensional collagen gel contraction assay, we studied the biophysical and structural properties of glomeruli and podocytes in chronic (Tg26 mice [HIV protein expression]) and acute (protamine administration [cytoskeletal rearrangement]) models of podocyte injury. Results Compared with wild-type glomeruli, Tg26 glomeruli became progressively more deformable with disease progression, despite increased collagen content. Tg26 podocytes had disordered cytoskeletons, markedly abnormal focal adhesions, and weaker adhesion; they failed to respond to mechanical signals and exerted minimal traction force in three-dimensional collagen gels. Protamine treatment had similar but milder effects on glomeruli and podocytes. Conclusions Reduced structural integrity of Tg26 podocytes causes increased deformability of glomerular capillaries and limits the ability of capillaries to counter hemodynamic force, possibly leading to further podocyte injury. Loss of normal podocyte mechanical integrity could injure neighboring podocytes due to the absence of normal biophysical signals required for podocyte maintenance. The severe defects in podocyte mechanical behavior in the Tg26 model may explain why Tg26 glomeruli soften progressively, despite increased collagen deposition, and may be the basis for the rapid course of glomerular diseases associated with severe podocyte injury. In milder injury (protamine), similar processes occur but over a longer time. Copyright © 2018 by the American Society of Nephrology.

  6. Fellowship | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Date of birth: 7 July 1939. Specialization: Structural Biology, Membrane Biophysics and Molecular Biophysics Address: Emeritus Professor, Molecular Biophysics Unit, Indian Institute of Science, Bengaluru 560 012, Karnataka Contact: Residence: (080) 4094 3455. Mobile: 99866 22397. Email: krk_easwaran@yahoo.com, ...

  7. The role of bio-physical cohesive substrates on sediment winnowing and bedform development

    Science.gov (United States)

    Ye, Leiping; Parsons, Daniel; Manning, Andrew

    2017-04-01

    Existing sediment transport and bedform size predictions for natural open-channel flows in many environments are seriously impeded by a lack of process-based knowledge concerning the dynamics of complex bed sediment mixtures comprising cohesionless sand and biologically-active cohesive muds. A series of flume experiments (14 experimental runs) with different substrate mixtures of sand-clay-EPS (Extracellular Polymeric Substance) are combined with a detailed estuarine field survey (Dee estuary, NW England) to investigate the development of bedform morphologies and characteristics of suspended sediment over bio-physical cohesive substrates. The experimental results indicate that winnowing and sediment sorting can occur pervasively in bio-physical cohesive sediment - flow systems. Importantly however, the evolution of the bed and bedform dynamics, and hence turbulence production, is significantly reduced as bed substrate cohesivity increases. The estuarine subtidal zone survey also revealed that the bio-physical cohesion provided by both the clay and microorganism fractions in the bed plays a significant role in controlling the interactions between bed substrate and sediment suspension, deposition and bedform generation. The work will be presented here concludes by outlining the need to extend and revisit the effects of cohesivity in morphodynamic systems and the sets of parameters presently used in numerical modelling, particularly in the context of the impact of climate change on estuarine and coastal systems.

  8. “Exosomics”—A Review of Biophysics, Biology and Biochemistry of Exosomes With a Focus on Human Breast Milk

    Directory of Open Access Journals (Sweden)

    Carolina de la Torre Gomez

    2018-03-01

    Full Text Available Exosomes are biomolecular nanostructures released from cells. They carry specific biomolecular information and are mainly researched for their exquisite properties as a biomarker source and delivery system. We introduce exosomes in the context of other extracellular vesicles, describe their biophysical isolation and characterisation and discuss their biochemical profiling. Motivated by our interest in early-life nutrition and health, and corresponding studies enrolling lactating mothers and their infants, we zoom into exosomes derived from human breast milk. We argue that these should be more extensively studied at proteomic and micronutrient profiling level, because breast milk exosomes provide a more specific window into breast milk quality from an immunological (proteomics and nutritional (micronutrient perspective. Such enhanced breast milk exosome profiling would thereby complement and enrich the more classical whole breast milk analysis and is expected to deliver more functional insights than the rather descriptive analysis of human milk, or larger fractions thereof, such as milk fat globule membrane. We substantiate our arguments by a bioinformatic analysis of two published proteomic data sets of human breast milk exosomes.

  9. Unusual Self-Assembly of the Recombinant Chlamydia trachomatis Major Outer Membrane Protein-Based Fusion Antigen CTH522 Into Protein Nanoparticles

    DEFF Research Database (Denmark)

    Rose, Fabrice; Karlsen, Kasper; Jensen, Pernille

    2018-01-01

    Sexually transmitted Chlamydia trachomatis (Ct) infects more than 100 million people annually, and untreated chlamydia infections can cause severe complications. Therefore, there is an urgent need for a chlamydia vaccine. The Ct major outer membrane protein (MOMP) is highly immunogenic but is a c......Sexually transmitted Chlamydia trachomatis (Ct) infects more than 100 million people annually, and untreated chlamydia infections can cause severe complications. Therefore, there is an urgent need for a chlamydia vaccine. The Ct major outer membrane protein (MOMP) is highly immunogenic...... but is a challenging vaccine candidate by being an integral membrane protein, and the immunogenicity depends on a correctly folded structure. We investigated the biophysical properties of the recombinant MOMP-based fusion antigen CTH522, which is tested in early human clinical trials. It consists of a truncated......-defined secondary structural elements, and no thermal transitions were measurable. Chemical unfolding resulted monomers that upon removal of the denaturant self-assembled into higher order structures, comparable to the structure of the native protein. The conformation of CTH522 in nanoparticles is thus not entirely...

  10. Point mutations in the transmembrane region of the clic1 ion channel selectively modify its biophysical properties.

    Directory of Open Access Journals (Sweden)

    Stefania Averaimo

    Full Text Available Chloride intracellular Channel 1 (CLIC1 is a metamorphic protein that changes from a soluble cytoplasmic protein into a transmembrane protein. Once inserted into membranes, CLIC1 multimerises and is able to form chloride selective ion channels. Whilst CLIC1 behaves as an ion channel both in cells and in artificial lipid bilayers, its structure in the soluble form has led to some uncertainty as to whether it really is an ion channel protein. CLIC1 has a single putative transmembrane region that contains only two charged residues: arginine 29 (Arg29 and lysine 37 (Lys37. As charged residues are likely to have a key role in ion channel function, we hypothesized that mutating them to neutral alanine to generate K37A and R29A CLIC1 would alter the electrophysiological characteristics of CLIC1. By using three different electrophysiological approaches: i single channel Tip-Dip in artificial bilayers using soluble recombinant CLIC1, ii cell-attached and iii whole-cell patch clamp recordings in transiently transfected HEK cells, we determined that the K37A mutation altered the single-channel conductance while the R29A mutation affected the single-channel open probability in response to variation in membrane potential. Our results show that mutation of the two charged amino acids (K37 and R29 in the putative transmembrane region of CLIC1 alters the biophysical properties of the ion channel in both artificial bilayers and cells. Hence these charged residues are directly involved in regulating its ion channel activity. This strongly suggests that, despite its unusual structure, CLIC1 itself is able to form a chloride ion channel.

  11. Active generation and propagation of Ca2+ signals within tunneling membrane nanotubes.

    Science.gov (United States)

    Smith, Ian F; Shuai, Jianwei; Parker, Ian

    2011-04-20

    A new mechanism of cell-cell communication was recently proposed after the discovery of tunneling nanotubes (TNTs) between cells. TNTs are membrane protrusions with lengths of tens of microns and diameters of a few hundred nanometers that permit the exchange of membrane and cytoplasmic constituents between neighboring cells. TNTs have been reported to mediate intercellular Ca(2+) signaling; however, our simulations indicate that passive diffusion of Ca(2+) ions alone would be inadequate for efficient transmission between cells. Instead, we observed spontaneous and inositol trisphosphate (IP(3))-evoked Ca(2+) signals within TNTs between cultured mammalian cells, which sometimes remained localized and in other instances propagated as saltatory waves to evoke Ca(2+) signals in a connected cell. Consistent with this, immunostaining showed the presence of both endoplasmic reticulum and IP(3) receptors along the TNT. We propose that IP(3) receptors may actively propagate intercellular Ca(2+) signals along TNTs via Ca(2+)-induced Ca(2+) release, acting as amplification sites to overcome the limitations of passive diffusion in a chemical analog of electrical transmission of action potentials. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  12. Anti-pulmonary fibrotic activity of salvianolic acid B was screened by a novel method based on the cyto-biophysical properties.

    Science.gov (United States)

    Liu, Miao; Zheng, Mingjing; Xu, Hanying; Liu, Lianqing; Li, Yanchun; Xiao, Wei; Li, Jianchun; Ma, Enlong

    Various methods have been used to evaluate anti-fibrotic activity of drugs. However, most of them are complicated, labor-intensive and lack of efficiency. This study was intended to develop a rapid method for anti-fibrotic drugs screening based on biophysical properties. A549 cells in vitro were stimulated with transforming growth factor-β1 (TGF-β1), and fibrogenesis was confirmed by conventional immunological assays. Meanwhile, the alterations of cyto-biophysical properties including morphology, roughness and stiffness were measured utilizing atomic force microscopy (AFM). It was found that fibrogenesis was accompanied with changes of cellular biophysical properties. TGF-β1-stimulated A549 cells became remarkably longer, rougher and stiffer than the control. Then, the effect of N-acetyl-L-cysteine (NAC) as a positive drug on ameliorating fibrogenesis in TGF-β1-stimulated A549 cells was verified respectively by immunological and biophysical markers. The result of Principal Component Analysis showed that stiffness was a leading index among all biophysical markers during fibrogenesis. Salvianolic acid B (SalB), a natural anti-oxidant, was detected by AFM to protect TGF-β1-stimulated A549 cells against stiffening. Then, SalB treatment was provided in preventive mode on a rat model of bleomycin (BLM) -induced pulmonary fibrosis. The results showed that SalB treatment significantly ameliorated BLM-induced histological alterations, blocked collagen accumulations and reduced α-SMA expression in lung tissues. All these results revealed the anti-pulmonary fibrotic activity of SalB. Detection of cyto-biophysical properties were therefore recommended as a rapid method for anti-pulmonary fibrotic drugs screening. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. 6th international conference on biophysics and synchrotron radiation. Program/Abstracts

    International Nuclear Information System (INIS)

    Pittroff, Connie; Strasser, Susan Barr

    1999-01-01

    This STI product consists of the Program/Abstracts book that was prepared for the participants in the Sixth International Conference on Biophysics and Synchrotron Radiation that was held August 4-8, 1998, at the Advanced Photon Source, Argonne National Laboratory. This book contains the full conference program and abstracts of the scientific presentations

  14. 6th international conference on biophysics and synchrotron radiation. Program/Abstracts

    Energy Technology Data Exchange (ETDEWEB)

    Pittroff, Connie; Strasser, Susan Barr [lead editors

    1999-08-03

    This STI product consists of the Program/Abstracts book that was prepared for the participants in the Sixth International Conference on Biophysics and Synchrotron Radiation that was held August 4-8, 1998, at the Advanced Photon Source, Argonne National Laboratory. This book contains the full conference program and abstracts of the scientific presentations.

  15. A synthesized biophysical and social vulnerability assessment for Taiwan

    Science.gov (United States)

    Lee, Yung-Jaan

    2017-11-01

    Taiwan, located in the Western Pacific, is a country that is one of the most vulnerable to disasters that are associated with the changing climate; it is located within the Ring of Fire, which is the most geologically active region in the world. The environmental and geological conditions in Taiwan are sensitive and vulnerable to such disasters. Owing to increasing urbanization in Taiwan, floods and climate-related disasters have taken an increasing toll on human lives. As global warming accelerates the rising of sea levels and increasing of the frequency of extreme weather events, disasters will continue to affect socioeconomic development and human conditions. Under such circumstances, researchers and policymakers alike must recognize the importance of providing useful knowledge concerning vulnerability, disaster recovery and resilience. Strategies for reducing vulnerability and climate-related disaster risks and for increasing resilience involve preparedness, mitigation and adaptation. In the last two decades, extreme climate events have caused severe flash floods, debris flows, landslides, and other disasters and have had negative effects of many sectors, including agriculture, infrastructure and health. Since climate change is expected to have a continued impact on socio-economic development, this work develops a vulnerability assessment framework that integrates both biophysical and social vulnerability and supports synthesized vulnerability analyses to identify vulnerable areas in Taiwan. Owing to its geographical, geological and climatic features, Taiwan is susceptible to earthquakes, typhoons, droughts and various induced disasters. Therefore, Taiwan has the urgent task of establishing a framework for assessing vulnerability as a planning and policy tool that can be used to identify not only the regions that require special attention but also hotspots in which efforts should be made to reduce vulnerability and the risk of climate-related disaster. To

  16. Quantify the Biophysical and Socioeconomic Drivers of Changes in Forest and Agricultural Land in South and Southeast Asia

    Science.gov (United States)

    Xu, X.; Jain, A. K.; Calvin, K. V.

    2017-12-01

    Due to the rapid socioeconomic development and biophysical factors, South and Southeast Asia (SSEA) has become a hotspot region of land use and land cover changes (LULCCs) in past few decades. Uncovering the drivers of LULCC is crucial for improving the understanding of LULCC processes. Due to the differences from spatiotemporal scales, methods and data sources in previous studies, the quantitative relationships between the LULCC activities and biophysical and socioeconomic drivers at the regional scale of SSEA have not been established. Here we present a comprehensive estimation of the biophysical and socioeconomic drivers of the major LULCC activities in SSEA: changes in forest and agricultural land. We used the Climate Change Initiative land cover data developed by European Space Agency to reveal the dynamics of forest and agricultural land from 1992 to 2015. Then we synthesized 200 publications about LULCC drivers at different spatial scales in SSEA to identify the major drivers of these LULCC activities. Corresponding representative variables of the major drivers were collected. The geographically weighted regression was employed to assess the spatiotemporally heterogeneous drivers of LULCC. Moreover, we validated our results with some national level case studies in SSEA. The results showed that both biophysical conditions such as terrain, soil, and climate, and socioeconomic factors such as migration, poverty, and economy played important roles in driving the changes of forest and agricultural land. The major drivers varied in different locations and periods. Our study integrated the bottom-up knowledge from local scale case studies with the top-down estimation of LULCC drivers, therefore generated more accurate and credible results. The identified biophysical and socioeconomic components could be used to improve the LULCC modelling and projection.

  17. Biophysical and biochemical constraints imposed by salt stress:Learning from halophyte

    Directory of Open Access Journals (Sweden)

    Bernardo eDuarte

    2014-12-01

    Full Text Available Soil salinization is one of the most important factors impacting plant productivity. About 3.6 billion of the world’s 5.2 billion ha of agricultural dryland have already suffered erosion, degradation and salinization. Halophytes typically are considered as plants able to complete their life cycle in environments where the salt concentration is 200 mM NaCl or higher. Different strategies are known to overcome salt stress, as adaptation mechanisms from this type of plants. Salinity adjustment is a complex phenomenon characterized by both biochemical and biophysical adaptations. As photosynthesis is a prerequisite for biomass production, halophytes adapted their electronic transduction pathways and the entire energetic metabolism to overcome the salt excess. The maintenance of ionic homeostasis is in the basis of all cellular stress in particular in terms of redox potential and energy transduction. In the present work the biophysical mechanisms underlying energy capture and transduction in halophytes are discussed alongside with their relation to biochemical mechanisms, integrating data from photosystem light harvesting complexes, electronic transport chains to the quinone pools, carbon harvesting and energy dissipation metabolism.

  18. Indoor Fast Neutron Generator for Biophysical and Electronic Applications

    Science.gov (United States)

    Cannuli, A.; Caccamo, M. T.; Marchese, N.; Tomarchio, E. A.; Pace, C.; Magazù, S.

    2018-05-01

    This study focuses the attention on an indoor fast neutron generator for biophysical and electronic applications. More specifically, the findings obtained by several simulations with the MCNP Monte Carlo code, necessary for the realization of a shield for indoor measurements, are presented. Furthermore, an evaluation of the neutron spectrum modification caused by the shielding is reported. Fast neutron generators are a valid and interesting available source of neutrons, increasingly employed in a wide range of research fields, such as science and engineering. The employed portable pulsed neutron source is a MP320 Thermo Scientific neutron generator, able to generate 2.5 MeV neutrons with a neutron yield of 2.0 x 106 n/s, a pulse rate of 250 Hz to 20 KHz and a duty factor varying from 5% to 100%. The neutron generator, based on Deuterium-Deuterium nuclear fusion reactions, is employed in conjunction with a solid-state photon detector, made of n-type high-purity germanium (PINS-GMX by ORTEC) and it is mainly addressed to biophysical and electronic studies. The present study showed a proposal for the realization of a shield necessary for indoor applications for MP320 neutron generator, with a particular analysis of the transport of neutrons simulated with Monte Carlo code and described the two main lines of research in which the source will be used.

  19. Epigenetic Modulation of the Biophysical Properties of Drug-Resistant Cell Lipids to Restore Drug Transport and Endocytic Functions

    OpenAIRE

    Vijayaraghavalu, Sivakumar; Peetla, Chiranjeevi; Lu, Shan; Labhasetwar, Vinod

    2012-01-01

    In our recent studies exploring the biophysical characteristics of resistant cell lipids, and the role they play in drug transport, we demonstrated the difference of drug-resistant breast cancer cells from drug-sensitive cells in lipid composition and biophysical properties, suggesting that cancer cells acquire a drug-resistant phenotype through the alteration of lipid synthesis to inhibit intracellular drug transport to protect from cytotoxic effect. In cancer cells, epigenetic changes (e.g....

  20. Cell surface area and membrane folding in glioblastoma cell lines differing in PTEN and p53 status.

    Directory of Open Access Journals (Sweden)

    Simon Memmel

    Full Text Available Glioblastoma multiforme (GBM is characterized by rapid growth, invasion and resistance to chemo-/radiotherapy. The complex cell surface morphology with abundant membrane folds, microvilli, filopodia and other membrane extensions is believed to contribute to the highly invasive behavior and therapy resistance of GBM cells. The present study addresses the mechanisms leading to the excessive cell membrane area in five GBM lines differing in mutational status for PTEN and p53. In addition to scanning electron microscopy (SEM, the membrane area and folding were quantified by dielectric measurements of membrane capacitance using the single-cell electrorotation (ROT technique. The osmotic stability and volume regulation of GBM cells were analyzed by video microscopy. The expression of PTEN, p53, mTOR and several other marker proteins involved in cell growth and membrane synthesis were examined by Western blotting. The combined SEM, ROT and osmotic data provided independent lines of evidence for a large variability in membrane area and folding among tested GBM lines. Thus, DK-MG cells (wild type p53 and wild type PTEN exhibited the lowest degree of membrane folding, probed by the area-specific capacitance C m = 1.9 µF/cm(2. In contrast, cell lines carrying mutations in both p53 and PTEN (U373-MG and SNB19 showed the highest C m values of 3.7-4.0 µF/cm(2, which corroborate well with their heavily villated cell surface revealed by SEM. Since PTEN and p53 are well-known inhibitors of mTOR, the increased membrane area/folding in mutant GBM lines may be related to the enhanced protein and lipid synthesis due to a deregulation of the mTOR-dependent downstream signaling pathway. Given that membrane folds and extensions are implicated in tumor cell motility and metastasis, the dielectric approach presented here provides a rapid and simple tool for screening the biophysical cell properties in studies on targeting chemo- or radiotherapeutically the

  1. Biochemistry and biophysics of HIV-1 gp41 - membrane interactions and implications for HIV-1 envelope protein mediated viral-cell fusion and fusion inhibitor design.

    Science.gov (United States)

    Cai, Lifeng; Gochin, Miriam; Liu, Keliang

    2011-12-01

    Human immunodeficiency virus type 1 (HIV-1), the pathogen of acquired immunodeficiency syndrome (AIDS), causes ~2 millions death every year and still defies an effective vaccine. HIV-1 infects host cells through envelope protein - mediated virus-cell fusion. The transmembrane subunit of envelope protein, gp41, is the molecular machinery which facilitates fusion. Its ectodomain contains several distinguishing functional domains, fusion peptide (FP), Nterminal heptad repeat (NHR), C-terminal heptad repeat (CHR) and membrane proximal extracellular region (MPER). During the fusion process, FP inserts into the host cell membrane, and an extended gp41 prehairpin conformation bridges the viral and cell membranes through MPER and FP respectively. Subsequent conformational change of the unstable prehairpin results in a coiled-coil 6-helix bundle (6HB) structure formed between NHR and CHR. The energetics of 6HB formation drives membrane apposition and fusion. Drugs targeting gp41 functional domains to prevent 6HB formation inhibit HIV-1 infection. T20 (enfuvirtide, Fuzeon) was approved by the US FDA in 2003 as the first fusion inhibitor. It is a 36-residue peptide from the gp41 CHR, and it inhibits 6HB formation by targeting NHR and lipids. Development of new fusion inhibitors, especially small molecule drugs, is encouraged to overcome the shortcomings of T20 as a peptide drug. Hydrophobic characteristics and membrane association are critical for gp41 function and mechanism of action. Research in gp41-membrane interactions, using peptides corresponding to specific functional domains, or constructs including several interactive domains, are reviewed here to get a better understanding of gp41 mediated virus-cell fusion that can inform or guide the design of new HIV-1 fusion inhibitors.

  2. Quantifying Vegetation Biophysical Variables from Imaging Spectroscopy Data: A Review on Retrieval Methods

    Science.gov (United States)

    Verrelst, Jochem; Malenovský, Zbyněk; Van der Tol, Christiaan; Camps-Valls, Gustau; Gastellu-Etchegorry, Jean-Philippe; Lewis, Philip; North, Peter; Moreno, Jose

    2018-06-01

    An unprecedented spectroscopic data stream will soon become available with forthcoming Earth-observing satellite missions equipped with imaging spectroradiometers. This data stream will open up a vast array of opportunities to quantify a diversity of biochemical and structural vegetation properties. The processing requirements for such large data streams require reliable retrieval techniques enabling the spatiotemporally explicit quantification of biophysical variables. With the aim of preparing for this new era of Earth observation, this review summarizes the state-of-the-art retrieval methods that have been applied in experimental imaging spectroscopy studies inferring all kinds of vegetation biophysical variables. Identified retrieval methods are categorized into: (1) parametric regression, including vegetation indices, shape indices and spectral transformations; (2) nonparametric regression, including linear and nonlinear machine learning regression algorithms; (3) physically based, including inversion of radiative transfer models (RTMs) using numerical optimization and look-up table approaches; and (4) hybrid regression methods, which combine RTM simulations with machine learning regression methods. For each of these categories, an overview of widely applied methods with application to mapping vegetation properties is given. In view of processing imaging spectroscopy data, a critical aspect involves the challenge of dealing with spectral multicollinearity. The ability to provide robust estimates, retrieval uncertainties and acceptable retrieval processing speed are other important aspects in view of operational processing. Recommendations towards new-generation spectroscopy-based processing chains for operational production of biophysical variables are given.

  3. Assessment of the biophysical impacts of utility-scale photovoltaics through observations and modelling

    Science.gov (United States)

    Broadbent, A. M.; Georgescu, M.; Krayenhoff, E. S.; Sailor, D.

    2017-12-01

    Utility-scale solar power plants are a rapidly growing component of the solar energy sector. Utility-scale photovoltaic (PV) solar power generation in the United States has increased by 867% since 2012 (EIA, 2016). This expansion is likely to continue as the cost PV technologies decrease. While most agree that solar power can decrease greenhouse gas emissions, the biophysical effects of PV systems on surface energy balance (SEB), and implications for surface climate, are not well understood. To our knowledge, there has never been a detailed observational study of SEB at a utility-scale solar array. This study presents data from an eddy covariance observational tower, temporarily placed above a utility-scale PV array in Southern Arizona. Comparison of PV SEB with a reference (unmodified) site, shows that solar panels can alter the SEB and near surface climate. SEB observations are used to develop and validate a new and more complete SEB PV model. In addition, the PV model is compared to simpler PV modelling methods. The simpler PV models produce differing results to our newly developed model and cannot capture the more complex processes that influence PV SEB. Finally, hypothetical scenarios of PV expansion across the continental United States (CONUS) were developed using various spatial mapping criteria. CONUS simulations of PV expansion reveal regional variability in biophysical effects of PV expansion. The study presents the first rigorous and validated simulations of the biophysical effects of utility-scale PV arrays.

  4. Contributions of computational chemistry and biophysical techniques to fragment-based drug discovery.

    Science.gov (United States)

    Gozalbes, Rafael; Carbajo, Rodrigo J; Pineda-Lucena, Antonio

    2010-01-01

    In the last decade, fragment-based drug discovery (FBDD) has evolved from a novel approach in the search of new hits to a valuable alternative to the high-throughput screening (HTS) campaigns of many pharmaceutical companies. The increasing relevance of FBDD in the drug discovery universe has been concomitant with an implementation of the biophysical techniques used for the detection of weak inhibitors, e.g. NMR, X-ray crystallography or surface plasmon resonance (SPR). At the same time, computational approaches have also been progressively incorporated into the FBDD process and nowadays several computational tools are available. These stretch from the filtering of huge chemical databases in order to build fragment-focused libraries comprising compounds with adequate physicochemical properties, to more evolved models based on different in silico methods such as docking, pharmacophore modelling, QSAR and virtual screening. In this paper we will review the parallel evolution and complementarities of biophysical techniques and computational methods, providing some representative examples of drug discovery success stories by using FBDD.

  5. Biophysical and structural considerations for protein sequence evolution

    Directory of Open Access Journals (Sweden)

    Grahnen Johan A

    2011-12-01

    Full Text Available Abstract Background Protein sequence evolution is constrained by the biophysics of folding and function, causing interdependence between interacting sites in the sequence. However, current site-independent models of sequence evolutions do not take this into account. Recent attempts to integrate the influence of structure and biophysics into phylogenetic models via statistical/informational approaches have not resulted in expected improvements in model performance. This suggests that further innovations are needed for progress in this field. Results Here we develop a coarse-grained physics-based model of protein folding and binding function, and compare it to a popular informational model. We find that both models violate the assumption of the native sequence being close to a thermodynamic optimum, causing directional selection away from the native state. Sampling and simulation show that the physics-based model is more specific for fold-defining interactions that vary less among residue type. The informational model diffuses further in sequence space with fewer barriers and tends to provide less support for an invariant sites model, although amino acid substitutions are generally conservative. Both approaches produce sequences with natural features like dN/dS Conclusions Simple coarse-grained models of protein folding can describe some natural features of evolving proteins but are currently not accurate enough to use in evolutionary inference. This is partly due to improper packing of the hydrophobic core. We suggest possible improvements on the representation of structure, folding energy, and binding function, as regards both native and non-native conformations, and describe a large number of possible applications for such a model.

  6. Microwave Tissue Ablation: Biophysics, Technology and Applications

    Science.gov (United States)

    2010-01-01

    Microwave ablation is an emerging treatment option for many cancers, cardiac arrhythmias and other medical conditions. During treatment, microwaves are applied directly to tissues to produce rapid temperature elevations sufficient to produce immediate coagulative necrosis. The engineering design criteria for each application differ, with individual consideration for factors such as desired ablation zone size, treatment duration, and procedural invasiveness. Recent technological developments in applicator cooling, power control and system optimization for specific applications promise to increase the utilization of microwave ablation in the future. This article will review the basic biophysics of microwave tissue heating, provide an overview of the design and operation of current equipment, and outline areas for future research for microwave ablation. PMID:21175404

  7. Hydrodynamic and Membrane Binding Properties of Purified Rous Sarcoma Virus Gag Protein

    Energy Technology Data Exchange (ETDEWEB)

    Dick, Robert A.; Datta, Siddhartha A.K.; Nanda, Hirsh; Fang, Xianyang; Wen, Yi; Barros, Marilia; Wang, Yun-Xing; Rein, Alan; Vogt, Volker M. (NCI); (Cornell); (CM); (NIST)

    2016-05-06

    Previously, no retroviral Gag protein has been highly purified in milligram quantities and in a biologically relevant and active form. We have purified Rous sarcoma virus (RSV) Gag protein and in parallel several truncation mutants of Gag and have studied their biophysical properties and membrane interactionsin vitro. RSV Gag is unusual in that it is not naturally myristoylated. From its ability to assemble into virus-like particlesin vitro, we infer that RSV Gag is biologically active. By size exclusion chromatography and small-angle X-ray scattering, Gag in solution appears extended and flexible, in contrast to previous reports on unmyristoylated HIV-1 Gag, which is compact. However, by neutron reflectometry measurements of RSV Gag bound to a supported bilayer, the protein appears to adopt a more compact, folded-over conformation. At physiological ionic strength, purified Gag binds strongly to liposomes containing acidic lipids. This interaction is stimulated by physiological levels of phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and by cholesterol. However, unlike HIV-1 Gag, RSV Gag shows no sensitivity to acyl chain saturation. In contrast with full-length RSV Gag, the purified MA domain of Gag binds to liposomes only weakly. Similarly, both an N-terminally truncated version of Gag that is missing the MA domain and a C-terminally truncated version that is missing the NC domain bind only weakly. These results imply that NC contributes to membrane interactionin vitro, either by directly contacting acidic lipids or by promoting Gag multimerization.

    Retroviruses like HIV assemble at and bud from the plasma membrane of cells. Assembly requires the interaction between thousands of Gag molecules to form a lattice. Previous work indicated that lattice formation at the plasma membrane is influenced by the conformation of monomeric HIV. We have extended this work to the more tractable RSV Gag. Our

  8. Abstracts of the 9. Brazilian Congress of Biophysics, 2. Brazilian Congress of Pharmacology and Experimental Therapeutics and 19. Brazilian Congress of Physiology

    International Nuclear Information System (INIS)

    1984-01-01

    Abstracts about biophysics, pharmacology, experimental therapeutics and physiology are presented. The use of radioisotopes in radioassays involve topics like biophysics and renal physiology; central nervous system; endocrinology; animal and comparative physiology; general physiology, digestion and nutrition; general pharmacology. (M.A.C.) [pt

  9. Canopy-scale biophysical controls on transpiration and evaporation in the Amazon Basin

    DEFF Research Database (Denmark)

    Mallick, Kaniska; Trebs, Ivonne; Bøgh, Eva

    2016-01-01

    to directly quantify the canopy-scale biophysical controls on λET and λEE over multiple plant functional types (PFTs) in the Amazon Basin. Combining data from six LBA (Large-scale Biosphere-Atmosphere Experiment in Amazonia) eddy covariance tower sites and a TR-driven physically based modeling approach, we...

  10. From autopoiesis to neurophenomenology: Francisco Varela's exploration of the biophysics of being

    Directory of Open Access Journals (Sweden)

    DAVID RUDRAUF

    2003-01-01

    Full Text Available This paper reviews in detail Francisco Varela's work on subjectivity and consciousness in the biological sciences. His original approach to this "hard problem" presents a subjectivity that is radically intertwined with its biological and physical roots. It must be understood within the framework of his theory of a concrete, embodied dynamics, grounded in his general theory of autonomous systems. Through concepts and paradigms such as biological autonomy, embodiment and neurophenomenology, the article explores the multiple levels of circular causality assumed by Varela to play a fundamental role in the emergence of human experience. The concept of biological autonomy provides the necessary and sufficient conditions for characterizing biological life and identity as an emergent and circular self-producing process. Embodiment provides a systemic and dynamical framework for understanding how a cognitive -a mind- can arise in an organism in the midst of its operational cycles of internal regulation and ongoing sensorimotor coupling. Global subjective properties can emerge at different levels from the interactions of components and can reciprocally constrain local processes through an ongoing, recursive morphodynamics. Neurophenomenology is a supplementary step in the study of consciousness. Through a rigorous method, it advocates the careful examination of experience with first-person methodologies. It attempts to create heuristic mutual constraints between biophysical data and data produced by accounts of subjective experience. The aim is to explicitly ground the active and disciplined insight the subject has about his/her experience in a biophysical emergent process. Finally, we discuss Varela's essential contribution to our understanding of the generation of consciousness in the framework of what we call his "biophysics of being."

  11. Study of pH (low) insertion peptides (pHLIPs) interaction with lipid bilayer of membrane

    Science.gov (United States)

    Weerakkody, Dhammika

    . Understanding the molecular events that occur when a peptide inserts across a membrane, folds, or exits from it and unfolds provides crucial information for the development of new drug delivery agents, as well as improving our understanding of the first step of membrane-associate protein folding. The promise of exploiting tumor acidosis as a cancer biomarker has not been fully realized in clinical practice, even though the acidity has been a known property since the work of Otto Warburg nearly a century ago. The problem has been to find a practical way to target acidity. pHLIP reversibly folds and inserts across membranes in response to pH changes, and this discovery has led to a novel way to target acidic tissue. Steady state biophysical studies have revealed the molecular mechanism of pHLIP action, which is based on the increase of hydrophobicity of carboxyl groups when they become protonated under mildly acidic conditions, leading to peptide insertion into a membrane. It has been shown that pHLIP can target acidic tissue and selectively translocate polar, cell-impermeable molecules across membranes in response to low extracellular pH. As noted in the Molecular Imaging and Contrast Agent Database (MICAD) at NCBI, a pHLIP labeled with a fluorescent dye, or a PET- and SPECT- agents (64Cu-DOTA, 18F, 99Tc) is a marker for in vivo acidity. All prior studies in vivo were carried out with the WT-pHLIP sequence and showed that a good contrast and tumor to blood ratio can be achieved only more than 24 hours after pHLIP injection, when it has accumulated in the tumor and largely cleared from the blood. However, for the use of pHLIP-based radioactive imaging agents in the clinic, a more rapid background signal reduction is absolutely essential. We have conducted research in order to address this important need, to tune tumor targeting properties, and to broaden our understanding of the molecular mechanism of pHLIP action. A family of 16 pHLIP variants has been designed based on chemical

  12. Final report for Conference Support Grant "From Computational Biophysics to Systems Biology - CBSB12"

    Energy Technology Data Exchange (ETDEWEB)

    Hansmann, Ulrich H.E.

    2012-07-02

    This report summarizes the outcome of the international workshop From Computational Biophysics to Systems Biology (CBSB12) which was held June 3-5, 2012, at the University of Tennessee Conference Center in Knoxville, TN, and supported by DOE through the Conference Support Grant 120174. The purpose of CBSB12 was to provide a forum for the interaction between a data-mining interested systems biology community and a simulation and first-principle oriented computational biophysics/biochemistry community. CBSB12 was the sixth in a series of workshops of the same name organized in recent years, and the second that has been held in the USA. As in previous years, it gave researchers from physics, biology, and computer science an opportunity to acquaint each other with current trends in computational biophysics and systems biology, to explore venues of cooperation, and to establish together a detailed understanding of cells at a molecular level. The conference grant of $10,000 was used to cover registration fees and provide travel fellowships to selected students and postdoctoral scientists. By educating graduate students and providing a forum for young scientists to perform research into the working of cells at a molecular level, the workshop adds to DOE's mission of paving the way to exploit the abilities of living systems to capture, store and utilize energy.

  13. A Method Sustaining the Bioelectric, Biophysical, and Bioenergetic Function of Cultured Rabbit Atrial Cells

    Directory of Open Access Journals (Sweden)

    Noa Kirschner Peretz

    2017-08-01

    Full Text Available Culturing atrial cells leads to a loss in their ability to be externally paced at physiological rates and to maintain their shape. We aim to develop a culture method that sustains the shape of atrial cells along with their biophysical and bioenergetic properties in response to physiological pacing. We hypothesize that adding 2,3-Butanedione 2-monoxime (BDM, which inhibits contraction during the culture period, will preserve these biophysical and bioenergetic properties. Rabbit atrial cells were maintained in culture for 24 h in a medium enriched with a myofilament contraction inhibitor, BDM. The morphology and volume of the cells, including their ability to contract in response to 1–3 Hz electrical pacing, was maintained at the same level as fresh cells. Importantly, the cells could be successfully infected with a GFP adenovirus. Action potentials, Ca2+ transients, and local Ca2+ spark parameters were similar in the cultured and in fresh cells. Finally, these cultured cells' flavoprotein autofluorescence was maintained at a constant level in response to electrical pacing, a response similar to that of fresh cells. Thus, eliminating contraction during the culture period preserves the bioelectric, biophysical and bioenergetic properties of rabbit atrial myocytes. This method therefore has the potential to further improve our understanding of energetic and biochemical regulation in the atria.

  14. Biophysics of NASA radiation quality factors

    International Nuclear Information System (INIS)

    Cucinotta, Francis A.

    2015-01-01

    NASA has implemented new radiation quality factors (QFs) for projecting cancer risks from space radiation exposures to astronauts. The NASA QFs are based on particle track structure concepts with parameters derived from available radiobiology data, and NASA introduces distinct QFs for solid cancer and leukaemia risk estimates. The NASA model was reviewed by the US National Research Council and approved for use by NASA for risk assessment for International Space Station missions and trade studies of future exploration missions to Mars and other destinations. A key feature of the NASA QFs is to represent the uncertainty in the QF assessments and evaluate the importance of the QF uncertainty to overall uncertainties in cancer risk projections. In this article, the biophysical basis for the probability distribution functions representing QF uncertainties was reviewed, and approaches needed to reduce uncertainties were discussed. (author)

  15. Structural Interpretation of the Large Slowdown of Water Dynamics at Stacked Phospholipid Membranes for Decreasing Hydration Level: All-Atom Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Carles Calero

    2016-04-01

    Full Text Available Hydration water determines the stability and function of phospholipid membranes as well as the interaction of membranes with other molecules. Experiments and simulations have shown that water dynamics slows down dramatically as the hydration decreases, suggesting that the interfacial water that dominates the average dynamics at low hydration is slower than water away from the membrane. Here, based on all-atom molecular dynamics simulations, we provide an interpretation of the slowdown of interfacial water in terms of the structure and dynamics of water–water and water–lipid hydrogen bonds (HBs. We calculate the rotational and translational slowdown of the dynamics of water confined in stacked phospholipid membranes at different levels of hydration, from completely hydrated to poorly hydrated membranes. For all hydrations, we analyze the distribution of HBs and find that water–lipids HBs last longer than water–water HBs and that at low hydration most of the water is in the interior of the membrane. We also show that water–water HBs become more persistent as the hydration is lowered. We attribute this effect (i to HBs between water molecules that form, in turn, persistent HBs with lipids; (ii to the hindering of the H-bonding switching between water molecules due to the lower water density at the interface; and (iii to the higher probability of water–lipid HBs as the hydration decreases. Our interpretation of the large dynamic slowdown in water under dehydration is potentially relevant in understanding membrane biophysics at different hydration levels.

  16. Developing a physics expert identity in a biophysics research group

    Science.gov (United States)

    Rodriguez, Idaykis; Goertzen, Renee Michelle; Brewe, Eric; Kramer, Laird H.

    2015-06-01

    We investigate the development of expert identities through the use of the sociocultural perspective of learning as participating in a community of practice. An ethnographic case study of biophysics graduate students focuses on the experiences the students have in their research group meetings. The analysis illustrates how the communities of practice-based identity constructs of competencies characterize student expert membership. A microanalysis of speech, sound, tones, and gestures in video data characterize students' social competencies in the physics community of practice. Results provide evidence that students at different stages of their individual projects have opportunities to develop social competencies such as mutual engagement, negotiability of the repertoire, and accountability to the enterprises as they interact with group members. The biophysics research group purposefully designed a learning trajectory including conducting research and writing it for publication in the larger community of practice as a pathway to expertise. The students of the research group learn to become socially competent as specific experts of their project topic and methodology, ensuring acceptance, agency, and membership in their community of practice. This work expands research on physics expertise beyond the cognitive realm and has implications for how to design graduate learning experiences to promote expert identity development.

  17. Biophysical characterization and functional studies on calbindin-D28K: A vitamin D-induced calcium-binding protein

    International Nuclear Information System (INIS)

    Leathers, V.L.

    1989-01-01

    Vitamin D dependent calcium binding protein, or calbindin-D, is the principal protein induced in the intestine in response to the steroid hormone 1,25(OH) 2 -vitamin D 3 . A definitive role for calbindin-D in vitamin D 3 mediated biological responses remains unclear. Biophysical and functional studies on chick intestinal calbindin-D 28K (CaBP) were initiated so that some insight might be gained into its relevance to the process of intestinal calcium transport. Calbindin-D belongs to a class of high affinity calcium binding proteins which includes calmodulin, parvalbumin and troponin C. The Ca 2+ binding stoichiometry and binding constants for calbindin-D 28K were quantitated by Quin 2 titration analysis. The protein was found to bind 5-6 Ca 2+ ions with a K D on the order of 10 -8 , in agreement with the 6 domains identified from the amino acid sequence. A slow Ca 2+ exchange rate (80 s -1 ) as assessed by 43 Ca NMR and extensive calcium dependent conformational changes in 1 H NMR spectra were also observed. Functional studies on chick intestinal CaBP were carried out by two different methods. Interactions between CaBP and intestinal cellular components were assessed via photoaffinity labeling techniques. Specific calcium dependent complexes for CaBP were identified with bovine intestinal alkaline phosphatase and brush border membrane proteins of 60 and 150 kD. CaBP was also found to co-migrate with the alkaline phosphatase activity of chick intestinal brush border membranes as evaluated by gel filtration chromatography. The second procedure for evaluating CaBP functionality has involved the quantitation of CaBP association with vesicular transport components as assessed by ELISA. CaBP, immunoreactivity was observed in purified lysosomes, microsomes and microtubules

  18. Novel biophysical determination of miRNAs related to prostate and head and neck cancers

    Czech Academy of Sciences Publication Activity Database

    Hudcová, K.; Trnková, L.; Kejnovská, Iva; Vorlíčková, Michaela; Gumulec, J.; Kizek, R.; Masarik, M.

    2015-01-01

    Roč. 44, č. 3 (2015), s. 131-138 ISSN 0175-7571 Institutional support: RVO:68081707 Keywords : SQUAMOUS-CELL CARCINOMA * ELIMINATION VOLTAMMETRY * CYTOSINE SIGNALS Subject RIV: BO - Biophysics Impact factor: 1.444, year: 2015

  19. Ground-and satellite-based evidence of the biophysical mechanisms behind the greening Sahel

    DEFF Research Database (Denmark)

    Brandt, Martin Stefan; Mbow, Cheikh; Diouf, Abdoul A.

    2015-01-01

    After a dry period with prolonged droughts in the 1970s and 1980s, recent scientific outcome suggests that the decades of abnormally dry conditions in the Sahel have been reversed by positive anomalies in rainfall. Various remote sensing studies observed a positive trend in vegetation greenness...... over the last decades which is known as the re-greening of the Sahel. However, little investment has been made in including long-term ground-based data collections to evaluate and better understand the biophysical mechanisms behind these findings. Thus, deductions on a possible increment in biomass...... remain speculative. Our aim is to bridge these gaps and give specifics on the biophysical background factors of the re-greening Sahel. Therefore, a trend analysis was applied on long time series (1987-2013) of satellite-based vegetation and rainfall data, as well as on ground-observations of leaf biomass...

  20. Developing A Transdisciplinary Process and Community Partnerships to Anticipate Climate Change at the Local Level: The Role of Biophysical and Sociocultural Calendars

    Science.gov (United States)

    Kassam, K. A.; Samimi, C.; Trabucco, A.

    2017-12-01

    Difference is essential to solving the most complex problems faced by humanity. Anthropogenic climate change is one such "wicked problem" that demands cognitive diversity. Biophysical and social scientists must collaborate with scholars from the humanities to address practical issues of concern to local communities, which are at the forefront of impacts of climatic variation. As such, communities of inquirers (e.g. biophysical and social sciences, humanities) must work in tandem with communities of practice (e.g. farmers, fishers, gatherers, herders, hunters). This leads to co-generated knowledge where an adaptation strategy to climatic variation is locally grounded in the biophysical and sociocultural context of the communities where the impacts of climatic variation are most felt. We will present an innovative and `real time' example participatory and transdisciplinary research from an international project where we are developing integrated biophysical and sociocultural calendars, in short, ecological calendars, which are ecologically and culturally grounded in the local context to develop anticipatory capacity to anthropogenic climate change.

  1. Theory and simulations of adhesion receptor dimerization on membrane surfaces.

    Science.gov (United States)

    Wu, Yinghao; Honig, Barry; Ben-Shaul, Avinoam

    2013-03-19

    The equilibrium constants of trans and cis dimerization of membrane bound (2D) and freely moving (3D) adhesion receptors are expressed and compared using elementary statistical-thermodynamics. Both processes are mediated by the binding of extracellular subdomains whose range of motion in the 2D environment is reduced upon dimerization, defining a thin reaction shell where dimer formation and dissociation take place. We show that the ratio between the 2D and 3D equilibrium constants can be expressed as a product of individual factors describing, respectively, the spatial ranges of motions of the adhesive domains, and their rotational freedom within the reaction shell. The results predicted by the theory are compared to those obtained from a novel, to our knowledge, dynamical simulations methodology, whereby pairs of receptors perform realistic translational, internal, and rotational motions in 2D and 3D. We use cadherins as our model system. The theory and simulations explain how the strength of cis and trans interactions of adhesive receptors are affected both by their presence in the constrained intermembrane space and by the 2D environment of membrane surfaces. Our work provides fundamental insights as to the mechanism of lateral clustering of adhesion receptors after cell-cell contact and, more generally, to the formation of lateral microclusters of proteins on cell surfaces. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  2. Complex interplay between the P-glycoprotein multidrug efflux pump and the membrane: its role in modulating protein function

    Directory of Open Access Journals (Sweden)

    Frances Jane Sharom

    2014-03-01

    Full Text Available Multidrug resistance in cancer is linked to expression of the P-glycoprotein multidrug transporter (Pgp, ABCB1, which exports many structurally diverse compounds from cells. Substrates first partition into the bilayer and then interact with a large flexible binding pocket within the transporter’s transmembrane regions. Pgp has been described as a hydrophobic vacuum cleaner or an outwardly-directed drug/lipid flippase. Recent X-ray crystal structures have shed some light on the nature of the drug-binding pocket and suggested routes by which substrates can enter it from the membrane. Detergents have profound effects on Pgp function, and several appear to be substrates. Biochemical and biophysical studies in vitro, some using purified reconstituted protein, have explored the effects of the membrane environment. They have demonstrated that Pgp is involved in a complex relationship with its lipid environment, which modulates the behaviour of its substrates, as well as various functions of the protein, including ATP hydrolysis, drug binding and drug transport. Membrane lipid composition and fluidity, phospholipid headgroup and acyl chain length all influence Pgp function. Recent studies focusing on thermodynamics and kinetics have revealed some important principles governing Pgp-lipid and substrate-lipid interactions, and how these affect drug binding and transport. In some cells, Pgp is associated with cholesterol-rich microdomains which may modulate its functions. The relationship between Pgp and cholesterol remains an open question; however it clearly affects several aspects of its function in addition to substrate-membrane partitioning. The action of Pgp modulators appears to depend on their membrane permeability, and membrane fluidizers and surfactants reverse drug resistance, likely via an indirect mechanism. A detailed understanding of how the membrane affects Pgp substrates and Pgp’s catalytic cycle may lead to new strategies to combat

  3. An introduction to environmental biophysics

    CERN Document Server

    Campbell, Gaylon S

    1977-01-01

    The study of environmental biophysics probably began earlier in man's history than that of any other science. The study of organism-environment interaction provided a key to survival and progress. Systematic study of the science and recording of experimental results goes back many hundreds of years. Ben­ jamin Franklin, the early American statesman, inventor, printer, and scientist studied conduction, evaporation, and radiation. One of his observations is as follows: My desk on which I now write, and the lock of my desk, are both exposed to the same temperature of the air, and have therefore the same degree of heat or cold; yet if I lay my hand successively on the wood and on the metal, the latter feels much the coldest, not that it is really so, but being a better conductor, it more readily than the wood takes away and draws into itself the fire that was in my skin. 1 Franklin probably was not the first to discover this principle, and certainly was not the last. Modem researchers rediscover this principle f...

  4. Screening and large-scale expression of membrane proteins in mammalian cells for structural studies.

    Science.gov (United States)

    Goehring, April; Lee, Chia-Hsueh; Wang, Kevin H; Michel, Jennifer Carlisle; Claxton, Derek P; Baconguis, Isabelle; Althoff, Thorsten; Fischer, Suzanne; Garcia, K Christopher; Gouaux, Eric

    2014-11-01

    Structural, biochemical and biophysical studies of eukaryotic membrane proteins are often hampered by difficulties in overexpression of the candidate molecule. Baculovirus transduction of mammalian cells (BacMam), although a powerful method to heterologously express membrane proteins, can be cumbersome for screening and expression of multiple constructs. We therefore developed plasmid Eric Gouaux (pEG) BacMam, a vector optimized for use in screening assays, as well as for efficient production of baculovirus and robust expression of the target protein. In this protocol, we show how to use small-scale transient transfection and fluorescence-detection size-exclusion chromatography (FSEC) experiments using a GFP-His8-tagged candidate protein to screen for monodispersity and expression level. Once promising candidates are identified, we describe how to generate baculovirus, transduce HEK293S GnTI(-) (N-acetylglucosaminyltransferase I-negative) cells in suspension culture and overexpress the candidate protein. We have used these methods to prepare pure samples of chicken acid-sensing ion channel 1a (cASIC1) and Caenorhabditis elegans glutamate-gated chloride channel (GluCl) for X-ray crystallography, demonstrating how to rapidly and efficiently screen hundreds of constructs and accomplish large-scale expression in 4-6 weeks.

  5. Efficacy of betamethasone on the fetal motion and biophysical profile and amniotic fluid index in preterm fetuses.

    Science.gov (United States)

    Abbasalizadeh, Shamsi; Pharabar, Zahra Neghadan; Abbasalizadeh, Fatmeh; Ghojazadeh, Morteza; Goldust, Mohamad

    2013-11-15

    The term ofpreterm birth is used to define the premature neonates considering pregnancy age. In less than 34 week pregnancies, corticosteroids are prescribed to promote embryos' lung maturity. The presents study aimed at evaluating effects of betamethasone injection on feeling embryo motion by mother and index and biophysical profile in preterm pregnancies. In a descriptive-analytical study, 40 pregnant women with the pregnancy age of 30-34 weeks were evaluated. Embryo motion and index and biophysical profile of the amniotic fluid were checked before prescription of double dosage of muscular betamethasone (12 mg) at a 24 h time interval. The injection was repeated for 24 and 48 h after the first injection. The resulted outcomes were compared with those results related to before betamethasone injection. In this study, there was statistically meaningful relationship between embryo motions before injection of betamethasone and 12 h after its injection (p = 0.03). Also, there was a significant relationship between embryo motions 24 and 48 h after injection of betamethasone (p = 0.001). In other words, the embryo motions decreased 12 h after injection of betamethasone. They were improved 48 h after betamethasone injection. But, index and biophysical profile results of amniotic fluid were left unchanged. Application of betamethasone leads to evident but transient decrease in embryo motions. Although motion element of index and biophysical profile of amniotic fluid which is one of the tests used in evaluating the embryo health is fixed and normal, it can be concluded that injection of betamethasone may not affect embryo health.

  6. Analysis of the induction of the myelin basic protein binding to the plasma membrane phospholipid monolayer

    International Nuclear Information System (INIS)

    Zhang Lei; Hao Changchun; Feng Ying; Gao Feng; Lu Xiaolong; Li Junhua; Sun Runguang

    2016-01-01

    Myelin basic protein (MBP) is an essential structure involved in the generation of central nervous system (CNS) myelin. Myelin shape has been described as liquid crystal structure of biological membrane. The interactions of MBP with monolayers of different lipid compositions are responsible for the multi-lamellar structure and stability of myelin. In this paper, we have designed MBP-incorporated model lipid monolayers and studied the phase behavior of MBP adsorbed on the plasma membrane at the air/water interface by thermodynamic method and atomic force microscopy (AFM). By analyzing the pressure–area ( π – A ) and pressure–time ( π – T ) isotherms, univariate linear regression equation was obtained. In addition, the elastic modulus, surface pressure increase, maximal insertion pressure, and synergy factor of monolayers were detected. These parameters can be used to modulate the monolayers binding of protein, and the results show that MBP has the strongest affinity for 1,2-dipalmitoyl-sn-glycero-3- phosphoserine (DPPS) monolayer, followed by DPPC/DPPS mixed and 1,2-dipalmitoyl-sn-glycero-3-phospho-choline (DPPC) monolayers via electrostatic and hydrophobic interactions. AFM images of DPPS and DPPC/DPPS mixed monolayers in the presence of MBP (5 nM) show a phase separation texture at the surface pressure of 20 mN/m and the incorporation of MBP put into the DPPC monolayers has exerted a significant effect on the domain structure. MBP is not an integral membrane protein but, due to its positive charge, interacts with the lipid head groups and stabilizes the membranes. The interaction between MBP and phospholipid membrane to determine the nervous system of the disease has a good biophysical significance and medical value. (special topic)

  7. Outcome of Membrane Sweeping in Reducing Induction Rates in Post-Date Pregnancies

    International Nuclear Information System (INIS)

    Saleem, U.; Mustafa, N.; Akhtar, S.

    2013-01-01

    Objectives: To determine the effectiveness of membrane sweeping in reducing need for induction of labour in post-date pregnancies and to enlist types and frequencies of complications experienced with membrane sweeping. Study Design: Randomized Control trial. Setting and Duration of Study: The study was carried out at Department of Obstetrics and Gynaecology, Combined Military Hospital, Lahore from February 2007 to April 2008. Patients and Methods: One hundred primi or second gravidas with uncomplicated singleton pregnancies having cephalic presentation at 40+1-5 weeks of gestation were enrolled after informed consent, and divided randomly into two groups of fifty each. Biophysical profile of 8/8 for each case was ensured. Group A underwent membrane sweeping while group B did not. All patients not having spontaneous labour were induced at 40+5 weeks. Data regarding number of patients having spontaneous labour or induction of labour was recorded. Mode of delivery either vaginal or cesarean birth was also recorded. In group A occurence of complications i.e vaginal bleeding or leaking, discomfort, irregular pains, fever and neonatal sepsis was recorded. Results: The difference in rate of spontaneous labor, induction rate and mode of delivery was insignificant between both the groups (p>0.05). In group A, 44% felt discomfort, 4% had bleeding per vaginum, 2% had leaking per vaginum and 28% had more than one complication. There were no cases of maternal or neonatal sepsis. Twenty percent did not have any side effects. Conclusion: Sweeping of membranes is not effective in reducing induction rates in post dates pregnancies. It does not improve the spontaneous labour rate and there is no effect on the mode of delivery. Therefore, any potential benefits of this intervention must be balanced against risk of maternal discomfort and other adverse effects. (author)

  8. Introducing "biophysical redundancy": the global status and past evolution of unused water, land and productivity resources for food production

    Science.gov (United States)

    Fader, Marianela

    2017-04-01

    Countries have different resilience to sudden and long-term changes in food demand and supply. An important part of this resilience is the degree of biophysical redundancy, defined as the potential food production of 'spare land', available water resources (i.e., not already used for human activities), as well as production increases through yield gap closure on cultivated areas and potential agricultural areas. The presentation will show the results of a recently published paper1 on the evolution of biophysical redundancy for agricultural production at country level, from 1992 to 2012. Results indicate that in 2012, the biophysical redundancy of 75 (48) countries, mainly in North Africa, Western Europe, the Middle East and Asia, was insufficient to produce the caloric nutritional needs for at least 50% (25%) of their population during a year. Biophysical redundancy has decreased in the last two decades in 102 out of 155 countries, 11 of these went from high to limited redundancy, and nine of these from limited to very low redundancy. Although the variability of the drivers of change across different countries is high, improvements in yield and population growth have a clear impact on the decreases of redundancy towards the very low redundancy category. We took a more detailed look at countries classified as 'Low Income Economies (LIEs)' since they are particularly vulnerable to domestic or external food supply changes, due to their limited capacity to offset for food supply decreases with higher purchasing power on the international market. Currently, nine LIEs have limited or very low biophysical redundancy. Many of these showed a decrease in redundancy over the last two decades, which is not always linked with improvements in per capita food availability.

  9. Single Nucleobase Identification Using Biophysical Signatures from Nanoelectronic Quantum Tunneling.

    Science.gov (United States)

    Korshoj, Lee E; Afsari, Sepideh; Khan, Sajida; Chatterjee, Anushree; Nagpal, Prashant

    2017-03-01

    Nanoelectronic DNA sequencing can provide an important alternative to sequencing-by-synthesis by reducing sample preparation time, cost, and complexity as a high-throughput next-generation technique with accurate single-molecule identification. However, sample noise and signature overlap continue to prevent high-resolution and accurate sequencing results. Probing the molecular orbitals of chemically distinct DNA nucleobases offers a path for facile sequence identification, but molecular entropy (from nucleotide conformations) makes such identification difficult when relying only on the energies of lowest-unoccupied and highest-occupied molecular orbitals (LUMO and HOMO). Here, nine biophysical parameters are developed to better characterize molecular orbitals of individual nucleobases, intended for single-molecule DNA sequencing using quantum tunneling of charges. For this analysis, theoretical models for quantum tunneling are combined with transition voltage spectroscopy to obtain measurable parameters unique to the molecule within an electronic junction. Scanning tunneling spectroscopy is then used to measure these nine biophysical parameters for DNA nucleotides, and a modified machine learning algorithm identified nucleobases. The new parameters significantly improve base calling over merely using LUMO and HOMO frontier orbital energies. Furthermore, high accuracies for identifying DNA nucleobases were observed at different pH conditions. These results have significant implications for developing a robust and accurate high-throughput nanoelectronic DNA sequencing technique. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Biophysical influence of airborne carbon nanomaterials on natural pulmonary surfactant.

    Science.gov (United States)

    Valle, Russell P; Wu, Tony; Zuo, Yi Y

    2015-05-26

    Inhalation of nanoparticles (NP), including lightweight airborne carbonaceous nanomaterials (CNM), poses a direct and systemic health threat to those who handle them. Inhaled NP penetrate deep pulmonary structures in which they first interact with the pulmonary surfactant (PS) lining at the alveolar air-water interface. In spite of many research efforts, there is a gap of knowledge between in vitro biophysical study and in vivo inhalation toxicology since all existing biophysical models handle NP-PS interactions in the liquid phase. This technical limitation, inherent in current in vitro methodologies, makes it impossible to simulate how airborne NP deposit at the PS film and interact with it. Existing in vitro NP-PS studies using liquid-suspended particles have been shown to artificially inflate the no-observed adverse effect level of NP exposure when compared to in vivo inhalation studies and international occupational exposure limits (OELs). Here, we developed an in vitro methodology called the constrained drop surfactometer (CDS) to quantitatively study PS inhibition by airborne CNM. We show that airborne multiwalled carbon nanotubes and graphene nanoplatelets induce a concentration-dependent PS inhibition under physiologically relevant conditions. The CNM aerosol concentrations controlled in the CDS are comparable to those defined in international OELs. Development of the CDS has the potential to advance our understanding of how submicron airborne nanomaterials affect the PS lining of the lung.

  11. Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

    NARCIS (Netherlands)

    Denning, Denise; Roos, Wouter H

    2016-01-01

    The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a

  12. Temporal measurement and analysis of high-resolution spectral signatures of plants and relationships to biophysical characteristics

    Science.gov (United States)

    Bostater, Charles R., Jr.; Rebbman, Jan; Hall, Carlton; Provancha, Mark; Vieglais, David

    1995-11-01

    Measurements of temporal reflectance signatures as a function of growing season for sand live oak (Quercus geminata), myrtle oak (Q. myrtifolia, and saw palmetto (Serenoa repens) were collected during a two year study period. Canopy level spectral reflectance signatures, as a function of 252 channels between 368 and 1115 nm, were collected using near nadir viewing geometry and a consistent sun illumination angle. Leaf level reflectance measurements were made in the laboratory using a halogen light source and an environmental optics chamber with a barium sulfate reflectance coating. Spectral measurements were related to several biophysical measurements utilizing optimal passive ambient correlation spectroscopy (OPACS) technique. Biophysical parameters included percent moisture, water potential (MPa), total chlorophyll, and total Kjeldahl nitrogen. Quantitative data processing techniques were used to determine optimal bands based on the utilization of a second order derivative or inflection estimator. An optical cleanup procedure was then employed that computes the double inflection ratio (DIR) spectra for all possible three band combinations normalized to the previously computed optimal bands. These results demonstrate a unique approach to the analysis of high spectral resolution reflectance signatures for estimation of several biophysical measures of plants at the leaf and canopy level from optimally selected bands or bandwidths.

  13. Biophysics at the Boundaries: The Next Problem Sets

    Science.gov (United States)

    Skolnick, Malcolm

    2009-03-01

    The interface between physics and biology is one of the fastest growing subfields of physics. As knowledge of such topics as cellular processes and complex ecological systems advances, researchers have found that progress in understanding these and other systems requires application of more quantitative approaches. Today, there is a growing demand for quantitative and computational skills in biological research and the commercialization of that research. The fragmented teaching of science in our universities still leaves biology outside the quantitative and mathematical culture that is the foundation of physics. This is particularly inopportune at a time when the needs for quantitative thinking about biological systems are exploding. More physicists should be encouraged to become active in research and development in the growing application fields of biophysics including molecular genetics, biomedical imaging, tissue generation and regeneration, drug development, prosthetics, neural and brain function, kinetics of nonequilibrium open biological systems, metabolic networks, biological transport processes, large-scale biochemical networks and stochastic processes in biochemical systems to name a few. In addition to moving into basic research in these areas, there is increasing opportunity for physicists in industry beginning with entrepreneurial roles in taking research results out of the laboratory and in the industries who perfect and market the inventions and developments that physicists produce. In this talk we will identify and discuss emerging opportunities for physicists in biophysical and biotechnological pursuits ranging from basic research through development of applications and commercialization of results. This will include discussion of the roles of physicists in non-traditional areas apart from academia such as patent law, financial analysis and regulatory science and the problem sets assigned in education and training that will enable future

  14. Biomechanical and biophysical environment of bone from the macroscopic to the pericellular and molecular level.

    Science.gov (United States)

    Ren, Li; Yang, Pengfei; Wang, Zhe; Zhang, Jian; Ding, Chong; Shang, Peng

    2015-10-01

    Bones with complicated hierarchical configuration and microstructures constitute the load-bearing system. Mechanical loading plays an essential role in maintaining bone health and regulating bone mechanical adaptation (modeling and remodeling). The whole-bone or sub-region (macroscopic) mechanical signals, including locomotion-induced loading and external actuator-generated vibration, ultrasound, oscillatory skeletal muscle stimulation, etc., give rise to sophisticated and distinct biomechanical and biophysical environments at the pericellular (microscopic) and collagen/mineral molecular (nanoscopic) levels, which are the direct stimulations that positively influence bone adaptation. While under microgravity, the stimulations decrease or even disappear, which exerts a negative influence on bone adaptation. A full understanding of the biomechanical and biophysical environment at different levels is necessary for exploring bone biomechanical properties and mechanical adaptation. In this review, the mechanical transferring theories from the macroscopic to the microscopic and nanoscopic levels are elucidated. First, detailed information of the hierarchical structures and biochemical composition of bone, which are the foundations for mechanical signal propagation, are presented. Second, the deformation feature of load-bearing bone during locomotion is clarified as a combination of bending and torsion rather than simplex bending. The bone matrix strains at microscopic and nanoscopic levels directly induced by bone deformation are critically discussed, and the strain concentration mechanism due to the complicated microstructures is highlighted. Third, the biomechanical and biophysical environments at microscopic and nanoscopic levels positively generated during bone matrix deformation or by dynamic mechanical loadings induced by external actuators, as well as those negatively affected under microgravity, are systematically discussed, including the interstitial fluid flow

  15. Direct interaction between EgFABP1, a fatty acid binding protein from Echinococcus granulosus, and phospholipid membranes.

    Directory of Open Access Journals (Sweden)

    Jorge L Porfido

    Full Text Available Growth and maintenance of hydatid cysts produced by Echinococcus granulosus have a high requirement for host lipids for biosynthetic processes, membrane building and possibly cellular and developmental signalling. This requires a high degree of lipid trafficking facilitated by lipid transporter proteins. Members of the fatty acid binding protein (FABP family have been identified in Echinococcus granulosus, one of which, EgFABP1 is expressed at the tegumental level in the protoscoleces, but it has also been described in both hydatid cyst fluid and secretions of protoscoleces. In spite of a considerable amount of structural and biophysical information on the FABPs in general, their specific functions remain mysterious.We have investigated the way in which EgFABP1 may interact with membranes using a variety of fluorescence-based techniques and artificial small unilamellar vesicles. We first found that bacterial recombinant EgFABP1 is loaded with fatty acids from the synthesising bacteria, and that fatty acid binding increases its resistance to proteinases, possibly due to subtle conformational changes induced on EgFABP1. By manipulating the composition of lipid vesicles and the ionic environment, we found that EgFABP1 interacts with membranes in a direct contact, collisional, manner to exchange ligand, involving both ionic and hydrophobic interactions. Moreover, we observed that the protein can compete with cytochrome c for association with the surface of small unilamellar vesicles (SUVs.This work constitutes a first approach to the understanding of protein-membrane interactions of EgFABP1. The results suggest that this protein may be actively involved in the exchange and transport of fatty acids between different membranes and cellular compartments within the parasite.

  16. Biophysical and biomathematical adventures in radiobiology

    International Nuclear Information System (INIS)

    Scott, B.R.

    1991-01-01

    Highlights of my biophysical and biomathematical adventures in radiobiology is presented. Early adventures involved developing ''state-vector models'' for specific harmful effects (cell killing, life shortening) of exposure to radiation. More recent adventures led to developing ''hazard-function models'' for predicting biological effects (e.g., cell killing, mutations, tumor induction) of combined exposure to different toxicants. Hazard-function models were also developed for predicting harm to man from exposure to large radiation doses. Major conclusions derived from the modeling adventures are as follows: (1) synergistic effects of different genotoxic agents should not occur at low doses; (2) for exposure of the lung or bone marrow to large doses of photon radiation, low rates of exposure should be better tolerated than high rates; and (3) for some types of radiation (e.g., alpha particles and fission neutrons), moderate doses delivered at a low rate may be more harmful than the same dose given at a high rate. 53 refs., 7 figs

  17. Biophysics of NASA radiation quality factors.

    Science.gov (United States)

    Cucinotta, Francis A

    2015-09-01

    NASA has implemented new radiation quality factors (QFs) for projecting cancer risks from space radiation exposures to astronauts. The NASA QFs are based on particle track structure concepts with parameters derived from available radiobiology data, and NASA introduces distinct QFs for solid cancer and leukaemia risk estimates. The NASA model was reviewed by the US National Research Council and approved for use by NASA for risk assessment for International Space Station missions and trade studies of future exploration missions to Mars and other destinations. A key feature of the NASA QFs is to represent the uncertainty in the QF assessments and evaluate the importance of the QF uncertainty to overall uncertainties in cancer risk projections. In this article, the biophysical basis for the probability distribution functions representing QF uncertainties was reviewed, and approaches needed to reduce uncertainties were discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Predicting Variation of DNA Shape Preferences in Protein-DNA Interaction in Cancer Cells with a New Biophysical Model.

    Science.gov (United States)

    Batmanov, Kirill; Wang, Junbai

    2017-09-18

    DNA shape readout is an important mechanism of transcription factor target site recognition, in addition to the sequence readout. Several machine learning-based models of transcription factor-DNA interactions, considering DNA shape features, have been developed in recent years. Here, we present a new biophysical model of protein-DNA interactions by integrating the DNA shape properties. It is based on the neighbor dinucleotide dependency model BayesPI2, where new parameters are restricted to a subspace spanned by the dinucleotide form of DNA shape features. This allows a biophysical interpretation of the new parameters as a position-dependent preference towards specific DNA shape features. Using the new model, we explore the variation of DNA shape preferences in several transcription factors across various cancer cell lines and cellular conditions. The results reveal that there are DNA shape variations at FOXA1 (Forkhead Box Protein A1) binding sites in steroid-treated MCF7 cells. The new biophysical model is useful for elucidating the finer details of transcription factor-DNA interaction, as well as for predicting cancer mutation effects in the future.

  19. Fragility of complexity biophysical systems by neutron scattering

    Energy Technology Data Exchange (ETDEWEB)

    Magazu, Salvatore [Dipartimento di Fisica, Universita di Messina, P.O. Box 55, I-98166 Messina (Italy)]. E-mail: smagazu@unime.it; Migliardo, Federica [Dipartimento di Fisica, Universita di Messina, P.O. Box 55, I-98166 Messina (Italy); Bellocco, Ersilia [Dipartimento di Chimica Organica e Biologica, Universita di Messina, I-98166 Messina (Italy); Lagana, Giuseppina [Dipartimento di Chimica Organica e Biologica, Universita di Messina, I-98166 Messina (Italy); Mondelli, Claudia [CNR-INFM OGG and CRS-SOFT, c/o ILL, 6 Jules Horowitz, BP 156, 38042 Grenoble Cedex 9 (France)

    2006-11-15

    Neutron scattering is an exceptional tool to investigate structural and dynamical properties of systems of biophysical interest, such as proteins, enzymes, lipids and sugars. Moreover, elastic neutron scattering enhances the investigation of atomic motions in hydrated proteins in a wide temperature range and on the picosecond timescale. Homologous disaccharides, such as trehalose, maltose and sucrose, are cryptobiotic substances, since they allow to many organisms to undergo in a 'suspended life' state, known as cryptobiosis in extreme environmental conditions. The present paper is aimed to discuss the fragility degree of disaccharides, as evaluated of the temperature dependence of the mean square displacement by elastic neutron scattering, in order to link this feature with their bioprotective functions.

  20. On the biophysics and kinetics of toehold-mediated DNA strand displacement.

    Science.gov (United States)

    Srinivas, Niranjan; Ouldridge, Thomas E; Sulc, Petr; Schaeffer, Joseph M; Yurke, Bernard; Louis, Ard A; Doye, Jonathan P K; Winfree, Erik

    2013-12-01

    Dynamic DNA nanotechnology often uses toehold-mediated strand displacement for controlling reaction kinetics. Although the dependence of strand displacement kinetics on toehold length has been experimentally characterized and phenomenologically modeled, detailed biophysical understanding has remained elusive. Here, we study strand displacement at multiple levels of detail, using an intuitive model of a random walk on a 1D energy landscape, a secondary structure kinetics model with single base-pair steps and a coarse-grained molecular model that incorporates 3D geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Two factors explain the dependence of strand displacement kinetics on toehold length: (i) the physical process by which a single step of branch migration occurs is significantly slower than the fraying of a single base pair and (ii) initiating branch migration incurs a thermodynamic penalty, not captured by state-of-the-art nearest neighbor models of DNA, due to the additional overhang it engenders at the junction. Our findings are consistent with previously measured or inferred rates for hybridization, fraying and branch migration, and they provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems.

  1. Plasma membrane order and fluidity are diversely triggered by elicitors of plant defence.

    Science.gov (United States)

    Sandor, Roman; Der, Christophe; Grosjean, Kevin; Anca, Iulia; Noirot, Elodie; Leborgne-Castel, Nathalie; Lochman, Jan; Simon-Plas, Françoise; Gerbeau-Pissot, Patricia

    2016-09-01

    Although plants are exposed to a great number of pathogens, they usually defend themselves by triggering mechanisms able to limit disease development. Alongside signalling events common to most such incompatible interactions, modifications of plasma membrane (PM) physical properties could be new players in the cell transduction cascade. Different pairs of elicitors (cryptogein, oligogalacturonides, and flagellin) and plant cells (tobacco and Arabidopsis) were used to address the issue of possible modifications of plant PM biophysical properties induced by elicitors and their links to other events of the defence signalling cascade. We observed an increase of PM order whatever the elicitor/plant cell pair used, provided that a signalling cascade was induced. Such membrane modification is dependent on the NADPH oxidase-mediated reactive oxygen species production. Moreover, cryptogein, which is the sole elicitor able to trap sterols, is also the only one able to trigger an increase in PM fluidity. The use of cryptogein variants with altered sterol-binding properties confirms the strong correlation between sterol removal from the PM and PM fluidity enhancement. These results propose PM dynamics as a player in early signalling processes triggered by elicitors of plant defence. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  2. Membranes, methods of making membranes, and methods of separating gases using membranes

    Science.gov (United States)

    Ho, W. S. Winston

    2012-10-02

    Membranes, methods of making membranes, and methods of separating gases using membranes are provided. The membranes can include at least one hydrophilic polymer, at least one cross-linking agent, at least one base, and at least one amino compound. The methods of separating gases using membranes can include contacting a gas stream containing at least one of CO.sub.2, H.sub.2S, and HCl with one side of a nonporous and at least one of CO.sub.2, H.sub.2S, and HCl selectively permeable membrane such that at least one of CO.sub.2, H.sub.2S, and HCl is selectively transported through the membrane.

  3. A multivariate decision tree analysis of biophysical factors in tropical forest fire occurrence

    Science.gov (United States)

    Rey S. Ofren; Edward Harvey

    2000-01-01

    A multivariate decision tree model was used to quantify the relative importance of complex hierarchical relationships between biophysical variables and the occurrence of tropical forest fires. The study site is the Huai Kha Kbaeng wildlife sanctuary, a World Heritage Site in northwestern Thailand where annual fires are common and particularly destructive. Thematic...

  4. Use of an integrated biophysical process for the treatment of halo- and nitro- organic wastes

    Directory of Open Access Journals (Sweden)

    Liron Shoshani

    2017-07-01

    Full Text Available This study assessed the use of an integrated biophysical process incorporating the addition of powdered activated carbon (PAC to a dual-sludge biological process, in order to improve the removal of problematic contaminants from complex herbicides production wastewater. The main focus was on the removal of nitrogen compounds, total organic carbon (TOC, and halogenated organics (AOX. The dual-sludge pilot setup comprised a conventional activated sludge (CAS system followed by a membrane bioreactor (MBR system. The dilution ratio of raw wastewater was gradually decreased (with groundwater from 0.8 to 0 (no dilution, and PAC was added in the last phase of the study to maintain an equilibrium concentration of 2000 mg/L. PAC addition stimulated a high and steady removal (98% of the ammoniacal nitrogen, conforming to the sea discharge limit of 5 mg/L. However, the effluent concentrations of total nitrogen, TOC, and AOX were still above the stringent discharge limits of 20, 100 and 0.5 mg/L respectively. Furthermore, it was shown that synergistic effect of various toxic organic compounds, rather than mineral salinity, was the major cause for the acute inhibitions of nitrification and AOX removal. The study showed that the proposed process can function as an efficient treatment system for the complex wastewater typically produced in the herbicide industry, however, it is recommended that complementary physico-chemical treatment steps be added to the treatment process.

  5. Lipid bilayer-bound conformation of an integral membrane beta barrel protein by multidimensional MAS NMR

    International Nuclear Information System (INIS)

    Eddy, Matthew T.; Su, Yongchao; Silvers, Robert; Andreas, Loren; Clark, Lindsay; Wagner, Gerhard; Pintacuda, Guido; Emsley, Lyndon; Griffin, Robert G.

    2015-01-01

    The human voltage dependent anion channel 1 (VDAC) is a 32 kDa β-barrel integral membrane protein that controls the transport of ions across the outer mitochondrial membrane. Despite the determination of VDAC solution and diffraction structures, a structural basis for the mechanism of its function is not yet fully understood. Biophysical studies suggest VDAC requires a lipid bilayer to achieve full function, motivating the need for atomic resolution structural information of VDAC in a membrane environment. Here we report an essential step toward that goal: extensive assignments of backbone and side chain resonances for VDAC in DMPC lipid bilayers via magic angle spinning nuclear magnetic resonance (MAS NMR). VDAC reconstituted into DMPC lipid bilayers spontaneously forms two-dimensional lipid crystals, showing remarkable spectral resolution (0.5–0.3 ppm for 13 C line widths and <0.5 ppm 15 N line widths at 750 MHz). In addition to the benefits of working in a lipid bilayer, several distinct advantages are observed with the lipid crystalline preparation. First, the strong signals and sharp line widths facilitated extensive NMR resonance assignments for an integral membrane β-barrel protein in lipid bilayers by MAS NMR. Second, a large number of residues in loop regions were readily observed and assigned, which can be challenging in detergent-solubilized membrane proteins where loop regions are often not detected due to line broadening from conformational exchange. Third, complete backbone and side chain chemical shift assignments could be obtained for the first 25 residues, which comprise the functionally important N-terminus. The reported assignments allow us to compare predicted torsion angles for VDAC prepared in DMPC 2D lipid crystals, DMPC liposomes, and LDAO-solubilized samples to address the possible effects of the membrane mimetic environment on the conformation of the protein. Concluding, we discuss the strengths and weaknesses of the reported

  6. Stearoyl-CoA Desaturase 1 Is a Key Determinant of Membrane Lipid Composition in 3T3-L1 Adipocytes.

    Directory of Open Access Journals (Sweden)

    Sergio Rodriguez-Cuenca

    Full Text Available Stearoyl-CoA desaturase 1 (SCD1 is a lipogenic enzyme important for the regulation of membrane lipid homeostasis; dysregulation likely contributes to obesity associated metabolic disturbances. SCD1 catalyses the Δ9 desaturation of 12-19 carbon saturated fatty acids to monounsaturated fatty acids. To understand its influence in cellular lipid composition we investigated the effect of genetic ablation of SCD1 in 3T3-L1 adipocytes on membrane microdomain lipid composition at the species-specific level. Using liquid chromatography/electrospray ionisation-tandem mass spectrometry, we quantified 70 species of ceramide, mono-, di- and trihexosylceramide, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, bis(monoacylglycerophosphate, phosphatidylinositol and cholesterol in 3T3-L1 adipocytes in which a 90% reduction in scd1 mRNA expression was achieved with siRNA. Cholesterol content was unchanged although decreases in other lipids resulted in cholesterol accounting for a higher proportion of lipid in the membranes. This was associated with decreased membrane lateral diffusion. An increased ratio of 24:0 to 24:1 in ceramide, mono- and dihexosylceramide, and sphingomyelin likely also contributed to this decrease in lateral diffusion. Of particular interest, we observed a decrease in phospholipids containing arachidonic acid. Given the high degree of structural flexibility of this acyl chain this will influence membrane lateral diffusion, and is likely responsible for the transcriptional activation of Lands' cycle enzymes lpcat3 and mboat7. Of relevance these profound changes in the lipidome were not accompanied by dramatic changes in gene expression in mature differentiated adipocytes, suggesting that adaptive homeostatic mechanisms to ensure partial maintenance of the biophysical properties of membranes likely occur at a post-transcriptional level.

  7. Application of dynamic membranes in anaerobic membranes in anaerobic membrane bioreactor systems

    NARCIS (Netherlands)

    Erşahin, M.E.

    2015-01-01

    Anaerobic membrane bioreactors (AnMBRs) physically ensure biomass retention by the application of a membrane filtration process. With growing application experiences from aerobic membrane bioreactors (MBRs), the combination of membrane and anaerobic processes has received much attention and become

  8. Maximum likelihood estimation of biophysical parameters of synaptic receptors from macroscopic currents

    Directory of Open Access Journals (Sweden)

    Andrey eStepanyuk

    2014-10-01

    Full Text Available Dendritic integration and neuronal firing patterns strongly depend on biophysical properties of synaptic ligand-gated channels. However, precise estimation of biophysical parameters of these channels in their intrinsic environment is complicated and still unresolved problem. Here we describe a novel method based on a maximum likelihood approach that allows to estimate not only the unitary current of synaptic receptor channels but also their multiple conductance levels, kinetic constants, the number of receptors bound with a neurotransmitter and the peak open probability from experimentally feasible number of postsynaptic currents. The new method also improves the accuracy of evaluation of unitary current as compared to the peak-scaled non-stationary fluctuation analysis, leading to a possibility to precisely estimate this important parameter from a few postsynaptic currents recorded in steady-state conditions. Estimation of unitary current with this method is robust even if postsynaptic currents are generated by receptors having different kinetic parameters, the case when peak-scaled non-stationary fluctuation analysis is not applicable. Thus, with the new method, routinely recorded postsynaptic currents could be used to study the properties of synaptic receptors in their native biochemical environment.

  9. Interactive Biophysics with Microswimmers: Education, Cloud Experimentation, Programmed Swarms, and Biotic Games

    Science.gov (United States)

    Riedel-Kruse, Ingmar

    Modern biotechnology gets increasingly powerful to manipulate and measure microscopic biophysical processes. Nevertheless, no platform exists to truly interact with these processes, certainly not with the convenience that we are accustomed to from our electronic smart devices. In my talk I will provide the rational for such Interactive Biotechnology and conceptualize its core component, the BPU (biotic processing unit), which is then connected to an according user interface. The biophysical phenomena currently featured on these platforms utilize the phototactic response of motile microorganisms, e.g., Euglena gracilis, resulting in spatio-temporal dynamics from the single cell to the self-organized multi-cellular scale. I will demonstrate multiple platforms, such as scalable biology cloud experimentation labs, tangible museum exhibits, biotic video games, low-cost interactive DIY kits using smartphones, and programming languages for swarm robotics. I will discuss applications for education as well as for professional and citizen science. Hence, we turn traditionally observational microscopy into an interactive experience. I was told that presenting in the educational section does not count against the ''one author - one talk policy'' - so I submit two abstracts. In case of conflict - please contact me: ingmar@stanford.edu.

  10. Mechanoresponsive stem cells to target cancer metastases through biophysical cues.

    Science.gov (United States)

    Liu, Linan; Zhang, Shirley X; Liao, Wenbin; Farhoodi, Henry P; Wong, Chi W; Chen, Claire C; Ségaliny, Aude I; Chacko, Jenu V; Nguyen, Lily P; Lu, Mengrou; Polovin, George; Pone, Egest J; Downing, Timothy L; Lawson, Devon A; Digman, Michelle A; Zhao, Weian

    2017-07-26

    Despite decades of effort, little progress has been made to improve the treatment of cancer metastases. To leverage the central role of the mechanoenvironment in cancer metastasis, we present a mechanoresponsive cell system (MRCS) to selectively identify and treat cancer metastases by targeting the specific biophysical cues in the tumor niche in vivo. Our MRCS uses mechanosensitive promoter-driven mesenchymal stem cell (MSC)-based vectors, which selectively home to and target cancer metastases in response to specific mechanical cues to deliver therapeutics to effectively kill cancer cells, as demonstrated in a metastatic breast cancer mouse model. Our data suggest a strong correlation between collagen cross-linking and increased tissue stiffness at the metastatic sites, where our MRCS is specifically activated by the specific cancer-associated mechano-cues. MRCS has markedly reduced deleterious effects compared to MSCs constitutively expressing therapeutics. MRCS indicates that biophysical cues, specifically matrix stiffness, are appealing targets for cancer treatment due to their long persistence in the body (measured in years), making them refractory to the development of resistance to treatment. Our MRCS can serve as a platform for future diagnostics and therapies targeting aberrant tissue stiffness in conditions such as cancer and fibrotic diseases, and it should help to elucidate mechanobiology and reveal what cells "feel" in the microenvironment in vivo. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  11. Quantitation of the calcium and membrane binding properties of the C2 domains of dysferlin.

    Science.gov (United States)

    Abdullah, Nazish; Padmanarayana, Murugesh; Marty, Naomi J; Johnson, Colin P

    2014-01-21

    Dysferlin is a large membrane protein involved in calcium-triggered resealing of the sarcolemma after injury. Although it is generally accepted that dysferlin is Ca(2+) sensitive, the Ca(2+) binding properties of dysferlin have not been characterized. In this study, we report an analysis of the Ca(2+) and membrane binding properties of all seven C2 domains of dysferlin as well as a multi-C2 domain construct. Isothermal titration calorimetry measurements indicate that all seven dysferlin C2 domains interact with Ca(2+) with a wide range of binding affinities. The C2A and C2C domains were determined to be the most sensitive, with Kd values in the tens of micromolar, whereas the C2D domain was least sensitive, with a near millimolar Kd value. Mutagenesis of C2A demonstrates the requirement for negatively charged residues in the loop regions for divalent ion binding. Furthermore, dysferlin displayed significantly lower binding affinity for the divalent cations magnesium and strontium. Measurement of a multidomain construct indicates that the solution binding affinity does not change when C2 domains are linked. Finally, sedimentation assays suggest all seven C2 domains bind lipid membranes, and that Ca(2+) enhances but is not required for interaction. This report reveals for the first time, to our knowledge, that all dysferlin domains bind Ca(2+) albeit with varying affinity and stoichiometry. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  12. The conformational stability and biophysical properties of the eukaryotic thioredoxins of Pisum sativum are not family-conserved.

    Directory of Open Access Journals (Sweden)

    David Aguado-Llera

    2011-02-01

    Full Text Available Thioredoxins (TRXs are ubiquitous proteins involved in redox processes. About forty genes encode TRX or TRX-related proteins in plants, grouped in different families according to their subcellular localization. For instance, the h-type TRXs are located in cytoplasm or mitochondria, whereas f-type TRXs have a plastidial origin, although both types of proteins have an eukaryotic origin as opposed to other TRXs. Herein, we study the conformational and the biophysical features of TRXh1, TRXh2 and TRXf from Pisum sativum. The modelled structures of the three proteins show the well-known TRX fold. While sharing similar pH-denaturations features, the chemical and thermal stabilities are different, being PsTRXh1 (Pisum sativum thioredoxin h1 the most stable isoform; moreover, the three proteins follow a three-state denaturation model, during the chemical-denaturations. These differences in the thermal- and chemical-denaturations result from changes, in a broad sense, of the several ASAs (accessible surface areas of the proteins. Thus, although a strong relationship can be found between the primary amino acid sequence and the structure among TRXs, that between the residue sequence and the conformational stability and biophysical properties is not. We discuss how these differences in the biophysical properties of TRXs determine their unique functions in pea, and we show how residues involved in the biophysical features described (pH-titrations, dimerizations and chemical-denaturations belong to regions involved in interaction with other proteins. Our results suggest that the sequence demands of protein-protein function are relatively rigid, with different protein-binding pockets (some in common for each of the three proteins, but the demands of structure and conformational stability per se (as long as there is a maintained core, are less so.

  13. Summaries of fiscal year 1994 projects in medical applications and biophysical research

    International Nuclear Information System (INIS)

    1995-04-01

    This report provides information on the research supported in Fiscal Year 1994 by the Medical Applications and Biophysical Research Division of the Office of Health and Environmental Research. A brief statement of the scope of the following areas is presented: dosimetry; measurement science; radiological and chemical physics; structural biology; human genome; and medical applications. Summaries of the research projects in these categories are presented

  14. Unraveling biophysical interactions of radiation pneumonitis in non-small-cell lung cancer via Bayesian network analysis.

    Science.gov (United States)

    Luo, Yi; El Naqa, Issam; McShan, Daniel L; Ray, Dipankar; Lohse, Ines; Matuszak, Martha M; Owen, Dawn; Jolly, Shruti; Lawrence, Theodore S; Kong, Feng-Ming Spring; Ten Haken, Randall K

    2017-04-01

    In non-small-cell lung cancer radiotherapy, radiation pneumonitis≥grade 2 (RP2) depends on patients' dosimetric, clinical, biological and genomic characteristics. We developed a Bayesian network (BN) approach to explore its potential for interpreting biophysical signaling pathways influencing RP2 from a heterogeneous dataset including single nucleotide polymorphisms, micro RNAs, cytokines, clinical data, and radiation treatment plans before and during the course of radiotherapy. Model building utilized 79 patients (21 with RP2) with complete data, and model testing used 50 additional patients with incomplete data. A developed large-scale Markov blanket approach selected relevant predictors. Resampling by k-fold cross-validation determined the optimal BN structure. Area under the receiver-operating characteristics curve (AUC) measured performance. Pre- and during-treatment BNs identified biophysical signaling pathways from the patients' relevant variables to RP2 risk. Internal cross-validation for the pre-BN yielded an AUC=0.82 which improved to 0.87 by incorporating during treatment changes. In the testing dataset, the pre- and during AUCs were 0.78 and 0.82, respectively. Our developed BN approach successfully handled a high number of heterogeneous variables in a small dataset, demonstrating potential for unraveling relevant biophysical features that could enhance prediction of RP2, although the current observations would require further independent validation. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Microscale Ocean Biophysics, Aspen Center for Physics: January 11-16 2015

    Science.gov (United States)

    2017-04-19

    dissolved   organic  matter  persist  in  the  deep  ocean:  Is  the  solution   dilution ?”     8.45  –  Kwangmin  Son...AUTHORS 7. PERFORMING ORGANIZATION NAMES AND ADDRESSES 15. SUBJECT TERMS b. ABSTRACT 2. REPORT TYPE 17. LIMITATION OF ABSTRACT 15. NUMBER OF PAGES...Microscale Ocean Biophysics, Aspen Center for Physics, January 11-16, 2015 Microscopic organisms control ocean processes at global scales. However

  16. Smart membranes for monitoring membrane based desalination processes

    KAUST Repository

    Laleg-Kirati, Taous-Meriem

    2017-10-12

    Various examples are related to smart membranes for monitoring membrane based process such as, e.g., membrane distillation processes. In one example, a membrane, includes a porous surface and a plurality of sensors (e.g., temperature, flow and/or impedance sensors) mounted on the porous surface. In another example, a membrane distillation (MD) process includes the membrane. Processing circuitry can be configured to monitor outputs of the plurality of sensors. The monitored outputs can be used to determine membrane degradation, membrane fouling, or to provide an indication of membrane replacement or cleaning. The sensors can also provide temperatures or temperature differentials across the porous surface, which can be used to improve modeling or control the MD process.

  17. PyFolding: Open-Source Graphing, Simulation, and Analysis of the Biophysical Properties of Proteins.

    Science.gov (United States)

    Lowe, Alan R; Perez-Riba, Albert; Itzhaki, Laura S; Main, Ewan R G

    2018-02-06

    For many years, curve-fitting software has been heavily utilized to fit simple models to various types of biophysical data. Although such software packages are easy to use for simple functions, they are often expensive and present substantial impediments to applying more complex models or for the analysis of large data sets. One field that is reliant on such data analysis is the thermodynamics and kinetics of protein folding. Over the past decade, increasingly sophisticated analytical models have been generated, but without simple tools to enable routine analysis. Consequently, users have needed to generate their own tools or otherwise find willing collaborators. Here we present PyFolding, a free, open-source, and extensible Python framework for graphing, analysis, and simulation of the biophysical properties of proteins. To demonstrate the utility of PyFolding, we have used it to analyze and model experimental protein folding and thermodynamic data. Examples include: 1) multiphase kinetic folding fitted to linked equations, 2) global fitting of multiple data sets, and 3) analysis of repeat protein thermodynamics with Ising model variants. Moreover, we demonstrate how PyFolding is easily extensible to novel functionality beyond applications in protein folding via the addition of new models. Example scripts to perform these and other operations are supplied with the software, and we encourage users to contribute notebooks and models to create a community resource. Finally, we show that PyFolding can be used in conjunction with Jupyter notebooks as an easy way to share methods and analysis for publication and among research teams. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  18. Recent advances on polymeric membranes for membrane reactors

    KAUST Repository

    Buonomenna, M. G.; Choi, Seung Hak

    2012-01-01

    . The successful use of membranes in membrane reactors is primary the result of two developments concerning: (i) membrane materials and (ii) membrane structures. The selection of a suited material and preparation technique depends on the application the membrane

  19. Functional and biophysical studies on four ceratoplatanins from the fungus Moniliophthora perniciosa, causal agent of the Witche's broom disease

    International Nuclear Information System (INIS)

    Barsottini, M.; Zaparoli, G.; Garcia, O.; Pereira, G.A.G.; Oliveira, J.F.; Tiezzi, H.O.; Ambrosio, A.L.B.; Dias, S.M.G.

    2012-01-01

    Full text: Ceratoplatanin (CP) is a secreted protein of 12.4 kDa initially identified in culture filtrates of the disease ascomycete Ceratocystis fimbriata f. sp. platani, etiological agent of the canker stain disease. CP is also the founding member of the namesake protein family, which contains fungal-secreted proteins involved in various stages of the host-fungus interaction and may act as phytotoxins or elicitors of defense response. Besides the low molecular weight, CPs have a high percentage of hydrophobic residues and share two conserved intramolecular disulfide bonds. It has been suggested that CPs have important physiological functions, including interaction with cell wall or cell membrane and manipulation of the host's defense system. Furthermore, a recent work showed that the ceratoplatanin from C. fimbriata has some degree of affinity for the saccharide 4-N-acetylglucosamine. However, its precise molecular function remains elusive. Five putative CPs have been identified in Moniliophthora perniciosa a basidiomycete fungus responsible for great economic losses in cocoa industry in the form of Witches' broom disease (WBD) , four of which had their crystal structures resolved by our group. In this work we report biophysical and functional studies on these MpCPs aiming at understanding their role and importance during the WBD progression. (author)

  20. Recent advances on polymeric membranes for membrane reactors

    KAUST Repository

    Buonomenna, M. G.

    2012-06-24

    Membrane reactors are generally applied in high temperature reactions (>400 °C). In the field of fine chemical synthesis, however, much milder conditions are generally applicable and polymeric membranes were applied without their damage. The successful use of membranes in membrane reactors is primary the result of two developments concerning: (i) membrane materials and (ii) membrane structures. The selection of a suited material and preparation technique depends on the application the membrane is to be used in. In this chapter a review of up to date literature about polymers and configuration catalyst/ membranes used in some recent polymeric membrane reactors is given. The new emerging concept of polymeric microcapsules as catalytic microreactors has been proposed. © 2012 Bentham Science Publishers. All rights reserved.

  1. Biophysics of skin and its treatments structural, nanotribological, and nanomechanical studies

    CERN Document Server

    Bhushan, Bharat

    2017-01-01

    This book provides a comprehensive overview of the structural, nanotribological and nanomechanical properties of skin with and without cream treatment as a function of operating environment. The biophysics of skin as the outer layer covering human or animal body is discussed as a complex biological structure. Skin cream is used to improve skin health and create a smooth, soft, and flexible surface with moist perception by altering the surface roughness, friction, adhesion, elastic modulus, and surface charge of the skin surface. .

  2. An ultra-sensitive biophysical risk assessment of light effect on skin cells.

    Science.gov (United States)

    Bennet, Devasier; Viswanath, Buddolla; Kim, Sanghyo; An, Jeong Ho

    2017-07-18

    The aim of this study was to analyze photo-dynamic and photo-pathology changes of different color light radiations on human adult skin cells. We used a real-time biophysical and biomechanics monitoring system for light-induced cellular changes in an in vitro model to find mechanisms of the initial and continuous degenerative process. Cells were exposed to intermittent, mild and intense (1-180 min) light with On/Off cycles, using blue, green, red and white light. Cellular ultra-structural changes, damages, and ECM impair function were evaluated by up/down-regulation of biophysical, biomechanical and biochemical properties. All cells exposed to different color light radiation showed significant changes in a time-dependent manner. Particularly, cell growth, stiffness, roughness, cytoskeletal integrity and ECM proteins of the human dermal fibroblasts-adult (HDF-a) cells showed highest alteration, followed by human epidermal keratinocytes-adult (HEK-a) cells and human epidermal melanocytes-adult (HEM-a) cells. Such changes might impede the normal cellular functions. Overall, the obtained results identify a new insight that may contribute to premature aging, and causes it to look aged in younger people. Moreover, these results advance our understanding of the different color light-induced degenerative process and help the development of new therapeutic strategies.

  3. Climate Change Effects on Agriculture: Economic Responses to Biophysical Shocks

    Science.gov (United States)

    Nelson, Gerald C.; Valin, Hugo; Sands, Ronald D.; Havlik, Petr; Ahammad, Helal; Deryng, Delphine; Elliott, Joshua; Fujimori, Shinichiro; Hasegawa, Tomoko; Heyhoe, Edwina

    2014-01-01

    Agricultural production is sensitive to weather and thus directly affected by climate change. Plausible estimates of these climate change impacts require combined use of climate, crop, and economic models. Results from previous studies vary substantially due to differences in models, scenarios, and data. This paper is part of a collective effort to systematically integrate these three types of models. We focus on the economic component of the assessment, investigating how nine global economic models of agriculture represent endogenous responses to seven standardized climate change scenarios produced by two climate and five crop models. These responses include adjustments in yields, area, consumption, and international trade. We apply biophysical shocks derived from the Intergovernmental Panel on Climate Change's representative concentration pathway with end-of-century radiative forcing of 8.5 W/m(sup 2). The mean biophysical yield effect with no incremental CO2 fertilization is a 17% reduction globally by 2050 relative to a scenario with unchanging climate. Endogenous economic responses reduce yield loss to 11%, increase area of major crops by 11%, and reduce consumption by 3%. Agricultural production, cropland area, trade, and prices show the greatest degree of variability in response to climate change, and consumption the lowest. The sources of these differences include model structure and specification; in particular, model assumptions about ease of land use conversion, intensification, and trade. This study identifies where models disagree on the relative responses to climate shocks and highlights research activities needed to improve the representation of agricultural adaptation responses to climate change.

  4. Drought propagation and its relation with catchment biophysical characteristics

    Science.gov (United States)

    Alvarez-Garreton, C. D.; Lara, A.; Garreaud, R. D.

    2016-12-01

    Droughts propagate in the hydrological cycle from meteorological to soil moisture to hydrological droughts. To understand the drivers of this process is of paramount importance since the economic and societal impacts in water resources are directly related with hydrological droughts (and not with meteorological droughts, which have been most studied). This research analyses drought characteristics over a large region and identify its main exogenous (climate forcing) and endogenous (biophysical characteristics such as land cover type and topography) explanatory factors. The study region is Chile, which covers seven major climatic subtypes according to Köppen system, it has unique geographic characteristics, very sharp topography and a wide range of landscapes and vegetation conditions. Meteorological and hydrological droughts (deficit in precipitation and streamflow, respectively) are characterized by their durations and standardized deficit volumes using a variable threshold method, over 300 representative catchments (located between 27°S and 50°S). To quantify the propagation from meteorological to hydrological drought, we propose a novel drought attenuation index (DAI), calculated as the ratio between the meteorological drought severity slope and the hydrological drought severity slope. DAI varies from zero (catchment that attenuates completely a meteorological drought) to one (the meteorological drought is fully propagated through the hydrological cycle). This novel index provides key (and comparable) information about drought propagation over a wide range of different catchments, which has been highlighted as a major research gap. Similar drought indicators across the wide range of catchments are then linked with catchment biophysical characteristics. A thorough compilation of land cover information (including the percentage of native forests, grass land, urban and industrial areas, glaciers, water bodies and no vegetated areas), catchment physical

  5. Membrane fouling mechanism of biofilm-membrane bioreactor (BF-MBR): Pore blocking model and membrane cleaning.

    Science.gov (United States)

    Zheng, Yi; Zhang, Wenxiang; Tang, Bing; Ding, Jie; Zheng, Yi; Zhang, Zhien

    2018-02-01

    Biofilm membrane bioreactor (BF-MBR) is considered as an important wastewater treatment technology that incorporates advantages of both biofilm and MBR process, as well as can alleviate membrane fouling, with respect to the conventional activated sludge MBR. But, to be efficient, it necessitates the establishment of proper methods for the assessment of membrane fouling. Four Hermia membrane blocking models were adopted to quantify and evaluate the membrane fouling of BF-MBR. The experiments were conducted with various operational conditions, including membrane types, agitation speeds and transmembrane pressure (TMP). Good agreement between cake formation model and experimental data was found, confirming the validity of the Hermia models for assessing the membrane fouling of BF-MBR and that cake layer deposits on membrane. Moreover, the influences of membrane types, agitation speeds and transmembrane pressure on the Hermia pore blocking coefficient of cake layer were investigated. In addition, the permeability recovery after membrane cleaning at various operational conditions was studied. This work confirms that, unlike conventional activated sludge MBR, BF-MBR possesses a low degree of membrane fouling and a higher membrane permeability recovery after cleaning. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Surface enhanced raman spectroscopy analytical, biophysical and life science applications

    CERN Document Server

    Schlücker, Sebastian

    2013-01-01

    Covering everything from the basic theoretical and practical knowledge to new exciting developments in the field with a focus on analytical and life science applications, this monograph shows how to apply surface-enhanced Raman scattering (SERS) for solving real world problems. From the contents: * Theory and practice of SERS * Analytical applications * SERS combined with other analytical techniques * Biophysical applications * Life science applications including various microscopies Aimed at analytical, surface and medicinal chemists, spectroscopists, biophysicists and materials scientists. Includes a Foreword by the renowned Raman spectroscopist Professor Wolfgang Kiefer, the former Editor-in-Chief of the Journal of Raman Spectroscopy.

  7. Hydrophobic ampersand hydrophilic: Theoretical models of solvation for molecular biophysics

    International Nuclear Information System (INIS)

    Pratt, L.R.; Tawa, G.J.; Hummer, G.; Garcia, A.E.; Corcelli, S.A.

    1996-01-01

    Molecular statistical thermodynamic models of hydration for chemistry and biophysics have advanced abruptly in recent years. With liquid water as solvent, salvation phenomena are classified as either hydrophobic or hydrophilic effects. Recent progress in treatment of hydrophilic effects have been motivated by continuum dielectric models interpreted as a modelistic implementation of second order perturbation theory. New results testing that perturbation theory of hydrophilic effects are presented and discussed. Recent progress in treatment of hydrophobic effects has been achieved by applying information theory to discover models of packing effects in dense liquids. The simplest models to which those ideas lead are presented and discussed

  8. The case for biophysics super-groups in physics departments.

    Science.gov (United States)

    Hoogenboom, Bart W; Leake, Mark

    2018-06-04

    Increasing numbers of physicists engage in research activities that address biological questions from physics perspectives or strive to develop physics insights from active biological processes. The on-going development and success of such activities morph our ways of thinking about what it is to 'do biophysics' and add to our understanding of the physics of life. Many scientists in this research and teaching landscape are homed in physics departments. A challenge for a hosting department is how to group, name and structure such biophysicists to best add value to their emerging research and teaching but also to the portfolio of the whole department. Here we discuss these issues and speculate on strategies. Creative Commons Attribution license.

  9. Biophysical properties and functional significance of stem water storage tissues in Neotropical savanna trees.

    Science.gov (United States)

    F.G. Scholz; S.J. Bucci; G. Goldstein; F.C. Meinzer; A.C. Franco; F. Miralles-Wilhelm

    2007-01-01

    Biophysical characteristics of sapwood and outer parenchyma water storage compartments were studied in stems of eight dominant Brazilian Cerrado tree species to assess the impact of differences in tissue capacitance on whole-plant water relations. Both the sapwood and outer parenchyma tissues played an important role in regulation of internal water deficits of Cerrado...

  10. Coupling the biophysical and social dimensions of wildfire risk to improve wildfire mitigation planning

    Science.gov (United States)

    Alan A. Ager; Jeffrey D. Kline; A. Paige Fisher

    2015-01-01

    We describe recent advances in biophysical and social aspects of risk and their potential combined contribution to improve mitigation planning on fire-prone landscapes. The methods and tools provide an improved method for defining the spatial extent of wildfire risk to communities compared to current planning processes. They also propose an expanded role for social...

  11. Membrane dynamics

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    Current topics include membrane-protein interactions with regard to membrane deformation or curvature sensing by BAR domains. Also, we study the dynamics of membrane tubes of both cells and simple model membrane tubes. Finally, we study membrane phase behavior which has important implications...... for the lateral organization of membranes as wells as for physical properties like bending, permeability and elasticity...

  12. Inverse colloidal crystal membranes for hydrophobic interaction membrane chromatography.

    Science.gov (United States)

    Vu, Anh T; Wang, Xinying; Wickramasinghe, S Ranil; Yu, Bing; Yuan, Hua; Cong, Hailin; Luo, Yongli; Tang, Jianguo

    2015-08-01

    Hydrophobic interaction membrane chromatography has gained interest due to its excellent performance in the purification of humanized monoclonal antibodies. The membrane material used in hydrophobic interaction membrane chromatography has typically been commercially available polyvinylidene fluoride. In this contribution, newly developed inverse colloidal crystal membranes that have uniform pores, high porosity and, therefore, high surface area for protein binding are used as hydrophobic interaction membrane chromatography membranes for humanized monoclonal antibody immunoglobulin G purification. The capacity of the inverse colloidal crystal membranes developed here is up to ten times greater than commercially available polyvinylidene fluoride membranes with a similar pore size. This work highlights the importance of developing uniform pore size high porosity membranes in order to maximize the capacity of hydrophobic interaction membrane chromatography. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

    OpenAIRE

    Xiao, Yun; Ahadian, Samad; Radisic, Milica

    2017-01-01

    Progress in biomaterial science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and controlling the cellular microenvironment of the wound tissue are important to improve the wound healing process. In this study, we review different bi...

  14. Polish Academy of Sciences. Institute of Biochemistry and Biophysics. Research Report 1998-1999

    International Nuclear Information System (INIS)

    2000-01-01

    The report presented research activities of the Institute of Biochemistry and Biophysics, Polish Academy of Sciences, in 1998-1999. Research interests focus on: replication, mutagenesis and repair of DNA, regulation of gene expression, biosynthesis and post-translational modifications of proteins, gene sequencing and functional gene analysis, structure and function of enzymes, conformation of proteins and peptides, modeling of structures and prediction of function of proteins

  15. Polish Academy of Sciences. Institute of Biochemistry and Biophysics. Research Report 1998-1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    The report presented research activities of the Institute of Biochemistry and Biophysics, Polish Academy of Sciences, in 1998-1999. Research interests focus on: replication, mutagenesis and repair of DNA, regulation of gene expression, biosynthesis and post-translational modifications of proteins, gene sequencing and functional gene analysis, structure and function of enzymes, conformation of proteins and peptides, modeling of structures and prediction of function of proteins.

  16. Smart membranes for monitoring membrane based desalination processes

    KAUST Repository

    Laleg-Kirati, Taous-Meriem; Karam, Ayman M.

    2017-01-01

    Various examples are related to smart membranes for monitoring membrane based process such as, e.g., membrane distillation processes. In one example, a membrane, includes a porous surface and a plurality of sensors (e.g., temperature, flow and

  17. Biomimetic membranes and methods of making biomimetic membranes

    Science.gov (United States)

    Rempe, Susan; Brinker, Jeffrey C.; Rogers, David Michael; Jiang, Ying-Bing; Yang, Shaorong

    2016-11-08

    The present disclosure is directed to biomimetic membranes and methods of manufacturing such membranes that include structural features that mimic the structures of cellular membrane channels and produce membrane designs capable of high selectivity and high permeability or adsorptivity. The membrane structure, material and chemistry can be selected to perform liquid separations, gas separation and capture, ion transport and adsorption for a variety of applications.

  18. Gel layer formation on membranes in Membrane Bioreactors

    NARCIS (Netherlands)

    Van den Brink, P.F.H.

    2014-01-01

    The widespread application of membrane bioreactors (MBRs) for municipal wastewater treatment is hampered by membrane fouling. Fouling increases energy demand, reduces process performance and creates the need for more frequent (chemical) membrane cleaning or replacement. Membrane fouling in MBRs is

  19. Towards Co-evolution of Membrane Transport and Metabolism

    Science.gov (United States)

    Wei, Chenyu; Pohorille, Andrzej

    2014-01-01

    Protocellular boundaries were inextricably connected to the metabolism they encapsulated: to be inheritable, early metabolism must have led to an increased rate of growth and division of vesicles and, similarly, transport through vesicle boundaries must have supported the evolution of metabolism. Even though explaining how this coupling emerged and evolved in the absence of the complex machinery of modern cells is one of the key issues in studies on the origin of life, little is known about the biochemical and biophysical processes that might have been involved. This gap in our knowledge is a major impediment in efforts to construct scenarios for the origin of life and laboratory models of protocells. A combination of experimental and computational studies carried out by us and our collaborators is aimed at helping to close this gap. Properties of membranes might have contributed to the selection of RNA as an early biopolymer. A kinetic mechanism was proposed (Sacerdote & Szostak, 2005) in which ribose was supplied more quickly than other aldopentoses to primordial cells for preferential incorporation of ribonucleotides into nucleic acids. This proposal is based on a finding that ribose permeates membranes an order of magnitude faster than its diastereomers, arabinose and xylose. Our computer simulations, which yield permeation rates in excellent agreement with experiment, and kinetic modeling explain this phenomenon in terms of inter- and intramolecular interactions involving exocyclic hydroxyl groups attached to carbon atoms of the pyranose ring (Wei and Pohorille, 2009). They also constrain scenarios for the formation of the earliest nucleic acids (Wei and Pohorille, 2013). In one scenario, sugars permeate protocellular walls and subsequently are used to synthesize nucleic acids inside protocells. As long as this process proceeds at the rate faster than 6x10(exp -3)/s, ribose derivatives will be available for synthesis easier than their diastereomers. If

  20. Nanodisc-solubilized membrane protein library reflects the membrane proteome.

    Science.gov (United States)

    Marty, Michael T; Wilcox, Kyle C; Klein, William L; Sligar, Stephen G

    2013-05-01

    The isolation and identification of unknown membrane proteins offers the prospect of discovering new pharmaceutical targets and identifying key biochemical receptors. However, interactions between membrane protein targets and soluble ligands are difficult to study in vitro due to the insolubility of membrane proteins in non-detergent systems. Nanodiscs, nanoscale discoidal lipid bilayers encircled by a membrane scaffold protein belt, have proven to be an effective platform to solubilize membrane proteins and have been used to study a wide variety of purified membrane proteins. This report details the incorporation of an unbiased population of membrane proteins from Escherichia coli membranes into Nanodiscs. This solubilized membrane protein library (SMPL) forms a soluble in vitro model of the membrane proteome. Since Nanodiscs contain isolated proteins or small complexes, the SMPL is an ideal platform for interactomics studies and pull-down assays of membrane proteins. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the protein population before and after formation of the Nanodisc library indicates that a large percentage of the proteins are incorporated into the library. Proteomic identification of several prominent bands demonstrates the successful incorporation of outer and inner membrane proteins into the Nanodisc library.

  1. Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity.

    Directory of Open Access Journals (Sweden)

    Christian Albers

    Full Text Available Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP. Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious and strong (teacher spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns.

  2. Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity.

    Science.gov (United States)

    Albers, Christian; Westkott, Maren; Pawelzik, Klaus

    2016-01-01

    Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP). Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious) and strong (teacher) spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns.

  3. On Biophysical Properties and Sensitivity to Gap Junction Blockers of Connexin 39 Hemichannels Expressed in HeLa Cells

    Science.gov (United States)

    Vargas, Anibal A.; Cisterna, Bruno A.; Saavedra-Leiva, Fujiko; Urrutia, Carolina; Cea, Luis A.; Vielma, Alex H.; Gutierrez-Maldonado, Sebastian E.; Martin, Alberto J. M.; Pareja-Barrueto, Claudia; Escalona, Yerko; Schmachtenberg, Oliver; Lagos, Carlos F.; Perez-Acle, Tomas; Sáez, Juan C.

    2017-01-01

    Although connexins (Cxs) are broadly expressed by cells of mammalian organisms, Cx39 has a very restricted pattern of expression and the biophysical properties of Cx39-based channels [hemichannels (HCs) and gap junction channels (GJCs)] remain largely unknown. Here, we used HeLa cells transfected with Cx39 (HeLa-Cx39 cells) in which intercellular electrical coupling was not detected, indicating the absence of GJCs. However, functional HCs were found on the surface of cells exposed to conditions known to increase the open probability of other Cx HCs (e.g., extracellular divalent cationic-free solution (DCFS), extracellular alkaline pH, mechanical stimulus and depolarization to positive membrane potentials). Cx39 HCs were blocked by some traditional Cx HC blockers, but not by others or a pannexin1 channel blocker. HeLa-Cx39 cells showed similar resting membrane potentials (RMPs) to those of parental cells, and exposure to DCFS reduced RMPs in Cx39 transfectants, but not in parental cells. Under these conditions, unitary events of ~75 pS were frequent in HeLa-Cx39 cells and absent in parental cells. Real-time cellular uptake experiments of dyes with different physicochemical features, as well as the application of a machine-learning approach revealed that Cx39 HCs are preferentially permeable to molecules characterized by six categories of descriptors, namely: (1) electronegativity, (2) ionization potential, (3) polarizability, (4) size and geometry, (5) topological flexibility and (6) valence. However, Cx39 HCs opened by mechanical stimulation or alkaline pH were impermeable to Ca2+. Molecular modeling of Cx39-based channels suggest that a constriction present at the intracellular portion of the para helix region co-localizes with an electronegative patch, imposing an energetic and steric barrier, which in the case of GJCs may hinder channel function. Results reported here demonstrate that Cx39 form HCs and add to our understanding of the functional roles of Cx39 HCs

  4. Fluctuation theory of solutions applications in chemistry, chemical engineering, and biophysics

    CERN Document Server

    Smith, Paul E

    2013-01-01

    There are essentially two theories of solutions that can be considered exact: the McMillan-Mayer theory and Fluctuation Solution Theory (FST). The first is mostly limited to solutes at low concentrations, while FST has no such issue. It is an exact theory that can be applied to any stable solution regardless of the number of components and their concentrations, and the types of molecules and their sizes. Fluctuation Theory of Solutions: Applications in Chemistry, Chemical Engineering, and Biophysics outlines the general concepts and theoretical basis of FST and provides a range of applications

  5. Flux Enhancement in Membrane Distillation Using Nanofiber Membranes

    Directory of Open Access Journals (Sweden)

    T. Jiříček

    2016-01-01

    Full Text Available Membrane distillation (MD is an emerging separation technology, whose largest application potential lies in the desalination of highly concentrated solutions, which are out of the scope of reverse osmosis. Despite many attractive features, this technology is still awaiting large industrial application. The main reason is the lack of commercially available membranes with fluxes comparable to reverse osmosis. MD is a thermal separation process driven by a partial vapour pressure difference. Flux, distillate purity, and thermal efficiency are always in conflict, all three being strictly connected with pore size, membrane hydrophobicity, and thickness. The world has not seen the ideal membrane yet, but nanofibers may offer a solution to these contradictory requirements. Membranes of electrospun PVDF were tested under various conditions on a direct contact (DCMD unit, in order to determine the optimum conditions for maximum flux. In addition, their performance was compared to commonly available PTFE, PE, and PES membranes. It was confirmed that thinner membranes have higher fluxes and a lower distillate purity and also higher energy losses via conduction across the membrane. As both mass and heat transfer are connected, it is best to develop new membranes with a target application in mind, for the specific membrane module and operational conditions.

  6. Fabrication of electrospun nanofibrous membranes for membrane distillation application

    KAUST Repository

    Francis, Lijo

    2013-02-01

    Nanofibrous membranes of Matrimid have been successfully fabricated using an electrospinning technique under optimized conditions. Nanofibrous membranes are found to be highly hydrophobic with a high water contact angle of 130°. Field emission scanning electron microscopy and pore size distribution analysis revealed the big pore size structure of electrospun membranes to be greater than 2 μm and the pore size distribution is found to be narrow. Flat sheet Matrimid membranes were fabricated via casting followed by phase inversion. The morphology, pore size distribution, and water contact angle were measured and compared with the electrospun membranes. Both membranes fabricated by electrospinning and phase inversion techniques were tested in a direct contact membrane distillation process. Electrospun membranes showed high water vapor flux of 56 kg/m2-h, which is very high compared to the casted membrane as well as most of the fabricated and commercially available highly hydrophobic membranes. ©2013 Desalination Publications.

  7. The physics, biophysics and technology of photodynamic therapy

    International Nuclear Information System (INIS)

    Wilson, Brian C; Patterson, Michael S

    2008-01-01

    Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components-light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT. (topical review)

  8. The physics, biophysics and technology of photodynamic therapy.

    Science.gov (United States)

    Wilson, Brian C; Patterson, Michael S

    2008-05-07

    Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components -- light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT.

  9. The physics, biophysics and technology of photodynamic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Brian C [Division of Biophysics and Bioimaging, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, ON M5G 2M9 (Canada); Patterson, Michael S [Department of Medical Physics, Juravinski Cancer Centre and Department of Medical Physics and Applied Radiation Sciences, McMaster University, 699 Concession Street, Hamilton, ON L8V 5C2 (Canada)], E-mail: wilson@uhnres.utoronto.ca, E-mail: mike.patterson@jcc.hhsc.ca

    2008-05-07

    Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components-light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT. (topical review)

  10. Biophysics

    International Nuclear Information System (INIS)

    Danyluk, S.S.

    1975-01-01

    Research is reported on magnetic resonance spectroscopy of biological molecules, development of clinical applications of stable isotopes, circadian cybernetics, and X-ray crystallography of immunoglobulins. Biological processes occur in fluid media, and ultimately our knowledge of their mechanisms requires detailed information for chemical and molecular structural properties in biological fluids. Magnetic resonance spectroscopy has unique advantages over other approaches in this area that are being exploited in studies currently underway in the group. The program continues to develop along three interrelated lines, measurement and analysis of high resolution spectra for biological molecules (especially nucleic acid constituents and drugs), synthesis of selectively labeled nucleic acid fragments essential for complete spectral assignments, and computation of conformational properties from NMR parameters. This coordinated approach enabled the first complete conformation analysis for a dinucleoside monophosphate, ApA, in aqueous solution. It was found that the conformation is actually a time-average of right helical, loop, and extended conformations, the interchange being extremely rapid on an NMR time scale. Spectral analyses were also completed for all possible ribonucleotide dimers, the assignments again relying heavily on synthesis of appropriate deuterated counterparts. Studies of conformational flexibility in nucleic acid fragments showed that changes in hydrogen ion concentration and temperature produce correlated conformational changes specific for each nucleotidyl unit. Studies were also initiated in three new projects dealing with the effect of hapten binding on antibody structure, counter ion influence on nucleic acid free radicals, and membrane differences between normal and sickled erythrocytes

  11. Alternative energy efficient membrane bioreactor using reciprocating submerged membrane.

    Science.gov (United States)

    Ho, J; Smith, S; Roh, H K

    2014-01-01

    A novel membrane bioreactor (MBR) pilot system, using membrane reciprocation instead of air scouring, was operated at constant high flux and daily fluctuating flux to demonstrate its application under peak and diurnal flow conditions. Low and stable transmembrane pressure was achieved at 40 l/m(2)/h (LMH) by use of repetitive membrane reciprocation. The results reveal that the inertial forces acting on the membrane fibers effectively propel foulants from the membrane surface. Reciprocation of the hollow fiber membrane is beneficial for the constant removal of solids that may build up on the membrane surface and inside the membrane bundle. The membrane reciprocation in the reciprocating MBR pilot consumed less energy than coarse air scouring used in conventional MBR systems. Specific energy consumption for the membrane reciprocation was 0.072 kWh/m(3) permeate produced at 40 LMH flux, which is 75% less than for a conventional air scouring system as reported in literature without consideration of energy consumption for biological aeration (0.29 kWh/m(3)). The daily fluctuating flux test confirmed that the membrane reciprocation is effective to handle fluctuating flux up to 50 LMH. The pilot-scale reciprocating MBR system successfully demonstrated that fouling can be controlled via 0.43 Hz membrane reciprocation with 44 mm or higher amplitude.

  12. Predicting membrane protein types using various decision tree classifiers based on various modes of general PseAAC for imbalanced datasets.

    Science.gov (United States)

    Sankari, E Siva; Manimegalai, D

    2017-12-21

    Predicting membrane protein types is an important and challenging research area in bioinformatics and proteomics. Traditional biophysical methods are used to classify membrane protein types. Due to large exploration of uncharacterized protein sequences in databases, traditional methods are very time consuming, expensive and susceptible to errors. Hence, it is highly desirable to develop a robust, reliable, and efficient method to predict membrane protein types. Imbalanced datasets and large datasets are often handled well by decision tree classifiers. Since imbalanced datasets are taken, the performance of various decision tree classifiers such as Decision Tree (DT), Classification And Regression Tree (CART), C4.5, Random tree, REP (Reduced Error Pruning) tree, ensemble methods such as Adaboost, RUS (Random Under Sampling) boost, Rotation forest and Random forest are analysed. Among the various decision tree classifiers Random forest performs well in less time with good accuracy of 96.35%. Another inference is RUS boost decision tree classifier is able to classify one or two samples in the class with very less samples while the other classifiers such as DT, Adaboost, Rotation forest and Random forest are not sensitive for the classes with fewer samples. Also the performance of decision tree classifiers is compared with SVM (Support Vector Machine) and Naive Bayes classifier. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. The Single Transmembrane Segment of Minimal Sensor DesK Senses Temperature via a Membrane-Thickness Caliper.

    Science.gov (United States)

    Inda, Maria E; Oliveira, Rafael G; de Mendoza, Diego; Cybulski, Larisa E

    2016-11-01

    as a consequence of temperature changes and activates a pathway to restore membrane fluidity at low temperature. Here, we demonstrated that membrane thickness variations do occur at physiological temperatures by directly measuring Bacillus lipid membrane thickness. We also dissected the N-terminal sensing motif of MS-DesK at the molecular-biophysical level and found that the dyad phenylalanine-lysine at the water-lipid phase is critical for achievement of a fine-tuned sensitivity to temperature. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Analysis of the induction of the myelin basic protein binding to the plasma membrane phospholipid monolayer

    Science.gov (United States)

    Zhang, Lei; Hao, Changchun; Feng, Ying; Gao, Feng; Lu, Xiaolong; Li, Junhua; Sun, Runguang

    2016-09-01

    Myelin basic protein (MBP) is an essential structure involved in the generation of central nervous system (CNS) myelin. Myelin shape has been described as liquid crystal structure of biological membrane. The interactions of MBP with monolayers of different lipid compositions are responsible for the multi-lamellar structure and stability of myelin. In this paper, we have designed MBP-incorporated model lipid monolayers and studied the phase behavior of MBP adsorbed on the plasma membrane at the air/water interface by thermodynamic method and atomic force microscopy (AFM). By analyzing the pressure-area (π-A) and pressure-time (π-T) isotherms, univariate linear regression equation was obtained. In addition, the elastic modulus, surface pressure increase, maximal insertion pressure, and synergy factor of monolayers were detected. These parameters can be used to modulate the monolayers binding of protein, and the results show that MBP has the strongest affinity for 1,2-dipalmitoyl-sn-glycero-3- phosphoserine (DPPS) monolayer, followed by DPPC/DPPS mixed and 1,2-dipalmitoyl-sn-glycero-3-phospho-choline (DPPC) monolayers via electrostatic and hydrophobic interactions. AFM images of DPPS and DPPC/DPPS mixed monolayers in the presence of MBP (5 nM) show a phase separation texture at the surface pressure of 20 mN/m and the incorporation of MBP put into the DPPC monolayers has exerted a significant effect on the domain structure. MBP is not an integral membrane protein but, due to its positive charge, interacts with the lipid head groups and stabilizes the membranes. The interaction between MBP and phospholipid membrane to determine the nervous system of the disease has a good biophysical significance and medical value. Project supported by the National Natural Science Foundation of China (Grant Nos. 21402114 and 11544009), the Natural Science Basic Research Plan in Shaanxi Province of China (Grant No. 2016JM2010), the Fundamental Research Funds for the Central

  15. Functional and biophysical studies on four ceratoplatanins from the fungus Moniliophthora perniciosa, causal agent of the Witche's broom disease

    Energy Technology Data Exchange (ETDEWEB)

    Barsottini, M.; Zaparoli, G.; Garcia, O.; Pereira, G.A.G. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Oliveira, J.F.; Tiezzi, H.O.; Ambrosio, A.L.B.; Dias, S.M.G. [Laboratorio Nacional de Biociencias - LNBIO, Campinas, SP (Brazil)

    2012-07-01

    Full text: Ceratoplatanin (CP) is a secreted protein of 12.4 kDa initially identified in culture filtrates of the disease ascomycete Ceratocystis fimbriata f. sp. platani, etiological agent of the canker stain disease. CP is also the founding member of the namesake protein family, which contains fungal-secreted proteins involved in various stages of the host-fungus interaction and may act as phytotoxins or elicitors of defense response. Besides the low molecular weight, CPs have a high percentage of hydrophobic residues and share two conserved intramolecular disulfide bonds. It has been suggested that CPs have important physiological functions, including interaction with cell wall or cell membrane and manipulation of the host's defense system. Furthermore, a recent work showed that the ceratoplatanin from C. fimbriata has some degree of affinity for the saccharide 4-N-acetylglucosamine. However, its precise molecular function remains elusive. Five putative CPs have been identified in Moniliophthora perniciosa a basidiomycete fungus responsible for great economic losses in cocoa industry in the form of Witches' broom disease (WBD) , four of which had their crystal structures resolved by our group. In this work we report biophysical and functional studies on these MpCPs aiming at understanding their role and importance during the WBD progression. (author)

  16. Constructing Precisely Computing Networks with Biophysical Spiking Neurons.

    Science.gov (United States)

    Schwemmer, Michael A; Fairhall, Adrienne L; Denéve, Sophie; Shea-Brown, Eric T

    2015-07-15

    While spike timing has been shown to carry detailed stimulus information at the sensory periphery, its possible role in network computation is less clear. Most models of computation by neural networks are based on population firing rates. In equivalent spiking implementations, firing is assumed to be random such that averaging across populations of neurons recovers the rate-based approach. Recently, however, Denéve and colleagues have suggested that the spiking behavior of neurons may be fundamental to how neuronal networks compute, with precise spike timing determined by each neuron's contribution to producing the desired output (Boerlin and Denéve, 2011; Boerlin et al., 2013). By postulating that each neuron fires to reduce the error in the network's output, it was demonstrated that linear computations can be performed by networks of integrate-and-fire neurons that communicate through instantaneous synapses. This left open, however, the possibility that realistic networks, with conductance-based neurons with subthreshold nonlinearity and the slower timescales of biophysical synapses, may not fit into this framework. Here, we show how the spike-based approach can be extended to biophysically plausible networks. We then show that our network reproduces a number of key features of cortical networks including irregular and Poisson-like spike times and a tight balance between excitation and inhibition. Lastly, we discuss how the behavior of our model scales with network size or with the number of neurons "recorded" from a larger computing network. These results significantly increase the biological plausibility of the spike-based approach to network computation. We derive a network of neurons with standard spike-generating currents and synapses with realistic timescales that computes based upon the principle that the precise timing of each spike is important for the computation. We then show that our network reproduces a number of key features of cortical networks

  17. Biophysical Properties of Cultivated Pastures in the Brazilian Savanna Biome: An Analysis in the Spatial-Temporal Domains Based on Ground and Satellite Data

    Directory of Open Access Journals (Sweden)

    Fernando M. Araújo

    2013-01-01

    Full Text Available Brazil has the largest commercial beef cattle herd in the world, with cattle ranching being particularly prominent in the 200-million ha, Brazilian neotropical moist savanna biome, known as Cerrado, one of the world’s hotspots for biodiversity conservation. As decreasing productivity is a major concern affecting the Cerrado pasturelands, evaluation of pasture conditions through the determination of biophysical parameters is instrumental for more effective management practices and herd occupation strategies. Within this context, the primary goal of this study was the regional assessment of pasture biophysical properties, through the scaling of wet- and dry-season ground truth data (total biomass, green biomass, and % green cover via the combined use of high (Landsat-TM and moderate (MODIS spatial resolution vegetation index images. Based on the high correlation found between NDVI (normalized difference vegetation index and % green cover (r = 0.95, monthly MODIS-based % green cover images were derived for the 2009–2010 hydrological cycle, which were able to capture major regional patterns and differences in pasture biophysical responses, including the increasing greenness values towards the southern portions of the biome, due to both local conditions (e.g., more fertile soils and management practices. These results corroborate the development of biophysically-based landscape degradation indices, in support of improved land use governance and natural area conservation in the Cerrado.

  18. Guidance for Large-scale Implementation of Alternate Wetting and Drying: A Biophysical Suitability Assessment

    Science.gov (United States)

    Sander, B. O.; Wassmann, R.; Nelson, A.; Palao, L.; Wollenberg, E.; Ishitani, M.

    2014-12-01

    The alternate wetting and drying (AWD) technology for rice production does not only save 15-30% of irrigation water, it also reduces methane emissions by up to 70%. AWD is defined by periodic drying and re-flooding of a rice field. Due to its high mitigation potential and its simplicity to execute this practice AWD has gained a lot of attention in recent years. The Climate and Clean Air Coalition (CCAC) has put AWD high on its agenda and funds a project to guide implementation of this technology in Vietnam, Bangladesh and Colombia. One crucial activity is a biophysical suitability assessment for AWD in the three countries. For this, we analyzed rainfall and soil data as well as potential evapotranspiration to assess if the water balance allows practicing AWD or if precipitation is too high for rice fields to fall dry. In my talk I will outline key factors for a successful large-scale implementation of AWD with a focus on the biophysical suitability assessment. The seasonal suitability maps that we generated highlight priority areas for AWD implementation and guide policy makers to informed decisions about meaningful investments in infrastructure and extension work.

  19. Giant plasma membrane vesicles: models for understanding membrane organization.

    Science.gov (United States)

    Levental, Kandice R; Levental, Ilya

    2015-01-01

    The organization of eukaryotic membranes into functional domains continues to fascinate and puzzle cell biologists and biophysicists. The lipid raft hypothesis proposes that collective lipid interactions compartmentalize the membrane into coexisting liquid domains that are central to membrane physiology. This hypothesis has proven controversial because such structures cannot be directly visualized in live cells by light microscopy. The recent observations of liquid-liquid phase separation in biological membranes are an important validation of the raft hypothesis and enable application of the experimental toolbox of membrane physics to a biologically complex phase-separated membrane. This review addresses the role of giant plasma membrane vesicles (GPMVs) in refining the raft hypothesis and expands on the application of GPMVs as an experimental model to answer some of key outstanding problems in membrane biology. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Membrane docking geometry of GRP1 PH domain bound to a target lipid bilayer: an EPR site-directed spin-labeling and relaxation study.

    Directory of Open Access Journals (Sweden)

    Huai-Chun Chen

    Full Text Available The second messenger lipid PIP(3 (phosphatidylinositol-3,4,5-trisphosphate is generated by the lipid kinase PI3K (phosphoinositide-3-kinase in the inner leaflet of the plasma membrane, where it regulates a broad array of cell processes by recruiting multiple signaling proteins containing PIP(3-specific pleckstrin homology (PH domains to the membrane surface. Despite the broad importance of PIP(3-specific PH domains, the membrane docking geometry of a PH domain bound to its target PIP(3 lipid on a bilayer surface has not yet been experimentally determined. The present study employs EPR site-directed spin labeling and relaxation methods to elucidate the membrane docking geometry of GRP1 PH domain bound to bilayer-embedded PIP(3. The model target bilayer contains the neutral background lipid PC and both essential targeting lipids: (i PIP(3 target lipid that provides specificity and affinity, and (ii PS facilitator lipid that enhances the PIP(3 on-rate via an electrostatic search mechanism. The EPR approach measures membrane depth parameters for 18 function-retaining spin labels coupled to the PH domain, and for calibration spin labels coupled to phospholipids. The resulting depth parameters, together with the known high resolution structure of the co-complex between GRP1 PH domain and the PIP(3 headgroup, provide sufficient constraints to define an optimized, self-consistent membrane docking geometry. In this optimized geometry the PH domain engulfs the PIP(3 headgroup with minimal bilayer penetration, yielding the shallowest membrane position yet described for a lipid binding domain. This binding interaction displaces the PIP(3 headgroup from its lowest energy position and orientation in the bilayer, but the headgroup remains within its energetically accessible depth and angular ranges. Finally, the optimized docking geometry explains previous biophysical findings including mutations observed to disrupt membrane binding, and the rapid lateral

  1. Benchmarking sensitivity of biophysical processes to leaf area changes in land surface models

    Science.gov (United States)

    Forzieri, Giovanni; Duveiller, Gregory; Georgievski, Goran; Li, Wei; Robestson, Eddy; Kautz, Markus; Lawrence, Peter; Ciais, Philippe; Pongratz, Julia; Sitch, Stephen; Wiltshire, Andy; Arneth, Almut; Cescatti, Alessandro

    2017-04-01

    Land surface models (LSM) are widely applied as supporting tools for policy-relevant assessment of climate change and its impact on terrestrial ecosystems, yet knowledge of their performance skills in representing the sensitivity of biophysical processes to changes in vegetation density is still limited. This is particularly relevant in light of the substantial impacts on regional climate associated with the changes in leaf area index (LAI) following the observed global greening. Benchmarking LSMs on the sensitivity of the simulated processes to vegetation density is essential to reduce their uncertainty and improve the representation of these effects. Here we present a novel benchmark system to assess model capacity in reproducing land surface-atmosphere energy exchanges modulated by vegetation density. Through a collaborative effort of different modeling groups, a consistent set of land surface energy fluxes and LAI dynamics has been generated from multiple LSMs, including JSBACH, JULES, ORCHIDEE, CLM4.5 and LPJ-GUESS. Relationships of interannual variations of modeled surface fluxes to LAI changes have been analyzed at global scale across different climatological gradients and compared with satellite-based products. A set of scoring metrics has been used to assess the overall model performances and a detailed analysis in the climate space has been provided to diagnose possible model errors associated to background conditions. Results have enabled us to identify model-specific strengths and deficiencies. An overall best performing model does not emerge from the analyses. However, the comparison with other models that work better under certain metrics and conditions indicates that improvements are expected to be potentially achievable. A general amplification of the biophysical processes mediated by vegetation is found across the different land surface schemes. Grasslands are characterized by an underestimated year-to-year variability of LAI in cold climates

  2. Polyurethane Nanofiber Membranes for Waste Water Treatment by Membrane Distillation

    Directory of Open Access Journals (Sweden)

    T. Jiříček

    2017-01-01

    Full Text Available Self-sustained electrospun polyurethane nanofiber membranes were manufactured and tested on a direct-contact membrane distillation unit in an effort to find the optimum membrane thickness to maximize flux rate and minimize heat losses across the membrane. Also salt retention and flux at high salinities up to 100 g kg−1 were evaluated. Even though the complex structure of nanofiber layers has extreme specific surface and porosity, membrane performance was surprisingly predictable; the highest flux was achieved with the thinnest membranes and the best energy efficiency was achieved with the thickest membranes. All membranes had salt retention above 99%. Nanotechnology offers the potential to find modern solutions for desalination of waste waters, by introducing new materials with revolutionary properties, but new membranes must be developed according to the target application.

  3. Warburg effect—damping of electromagnetic oscillations

    Czech Academy of Sciences Publication Activity Database

    Pokorný, Jiří; Pokorný, Jan; Borodavka, Fedir

    2017-01-01

    Roč. 36, č. 3 (2017), s. 270-278 ISSN 1536-8378 R&D Projects: GA ČR GA16-12757S Institutional support: RVO:68378271 Keywords : Warburg effect * mitochondrial dysfunction * water ordering * mitochondrial membrane potential * biological electromagnetic activity * cancer Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 1.272, year: 2016

  4. Fouling in Membrane Distillation, Osmotic Distillation and Osmotic Membrane Distillation

    Directory of Open Access Journals (Sweden)

    Mourad Laqbaqbi

    2017-03-01

    Full Text Available Various membrane separation processes are being used for seawater desalination and treatment of wastewaters in order to deal with the worldwide water shortage problem. Different types of membranes of distinct morphologies, structures and physico-chemical characteristics are employed. Among the considered membrane technologies, membrane distillation (MD, osmotic distillation (OD and osmotic membrane distillation (OMD use porous and hydrophobic membranes for production of distilled water and/or concentration of wastewaters for recovery and recycling of valuable compounds. However, the efficiency of these technologies is hampered by fouling phenomena. This refers to the accumulation of organic/inorganic deposits including biological matter on the membrane surface and/or in the membrane pores. Fouling in MD, OD and OMD differs from that observed in electric and pressure-driven membrane processes such electrodialysis (ED, membrane capacitive deionization (MCD, reverse osmosis (RO, nanofiltration (NF, ultrafiltration (UF, microfiltration (MF, etc. Other than pore blockage, fouling in MD, OD and OMD increases the risk of membrane pores wetting and reduces therefore the quantity and quality of the produced water or the concentration efficiency of the process. This review deals with the observed fouling phenomena in MD, OD and OMD. It highlights different detected fouling types (organic fouling, inorganic fouling and biofouling, fouling characterization techniques as well as various methods of fouling reduction including pretreatment, membrane modification, membrane cleaning and antiscalants application.

  5. Biophysical and biological contributions of polyamine-coated carbon nanotubes and bidimensional buckypapers in the delivery of miRNAs to human cells

    Directory of Open Access Journals (Sweden)

    Celluzzi A

    2017-12-01

    Full Text Available Antonella Celluzzi,1,* Alessandro Paolini,1,* Valentina D’Oria,1 Roberta Risoluti,2 Stefano Materazzi,2 Marco Pezzullo,1 Stefano Casciardi,3 Simona Sennato,4 Federico Bordi,4 Andrea Masotti1 1Bambino Gesù Children’s Hospital, IRCCS, Research Laboratories, 2Department of Chemistry, Sapienza University of Rome, 3Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, National Institution for Insurance Against Accidents at Work (INAIL Research, Monte Porzio Catone, 4CNR-ISC UOS Roma, Department of Physics, Sapienza University of Rome, Roma, Italy *These authors contributed equally to this work Abstract: Recent findings in nanomedicine have revealed that carbon nanotubes (CNTs can be used as potential drug carriers, therapeutic agents and diagnostics tools. Moreover, due to their ability to cross cellular membranes, their nanosize dimension, high surface area and relatively good biocompatibility, CNTs have also been employed as a novel gene delivery vector system. In our previous work, we functionalized CNTs with two polyamine polymers, polyethyleneimine (PEI and polyamidoamine dendrimer (PAMAM. These compounds have low cytotoxicity, ability to conjugate microRNAs (such as miR-503 and, at the same time, transfect efficiently endothelial cells. The parameters contributing to the good efficiency of transfection that we observed were not investigated in detail. In fact, the diameter and length of CNTs are important parameters to be taken into account when evaluating the effects on drug delivery efficiency. In order to investigate the biophysical and biological contributions of polymer-coated CNTs in delivery of miRNAs to human cells, we decided to investigate three different preparations, characterized by different dimensions and aspect ratios. In particular, we took into account very small CNTs, a suspension of CNTs starting from the commercial product and a 2D material based on CNTs (ie, buckypapers [BPs] to examine the

  6. Flow and fouling in membrane filters: Effects of membrane morphology

    Science.gov (United States)

    Sanaei, Pejman; Cummings, Linda J.

    2015-11-01

    Membrane filters are widely-used in microfiltration applications. Many types of filter membranes are produced commercially, for different filtration applications, but broadly speaking the requirements are to achieve fine control of separation, with low power consumption. The answer to this problem might seem obvious: select the membrane with the largest pore size and void fraction consistent with the separation requirements. However, membrane fouling (an inevitable consequence of successful filtration) is a complicated process, which depends on many parameters other than membrane pore size and void fraction; and which itself greatly affects the filtration process and membrane functionality. In this work we formulate mathematical models that can (i) account for the membrane internal morphology (internal structure, pore size & shape, etc.); (ii) fouling of membranes with specific morphology; and (iii) make some predictions as to what type of membrane morphology might offer optimum filtration performance.

  7. Association of lipidome remodeling in the adipocyte membrane with acquired obesity in humans.

    Directory of Open Access Journals (Sweden)

    Kirsi H Pietiläinen

    2011-06-01

    Full Text Available Identification of early mechanisms that may lead from obesity towards complications such as metabolic syndrome is of great interest. Here we performed lipidomic analyses of adipose tissue in twin pairs discordant for obesity but still metabolically compensated. In parallel we studied more evolved states of obesity by investigating a separated set of individuals considered to be morbidly obese. Despite lower dietary polyunsaturated fatty acid intake, the obese twin individuals had increased proportions of palmitoleic and arachidonic acids in their adipose tissue, including increased levels of ethanolamine plasmalogens containing arachidonic acid. Information gathered from these experimental groups was used for molecular dynamics simulations of lipid bilayers combined with dependency network analysis of combined clinical, lipidomics, and gene expression data. The simulations suggested that the observed lipid remodeling maintains the biophysical properties of lipid membranes, at the price, however, of increasing their vulnerability to inflammation. Conversely, in morbidly obese subjects, the proportion of plasmalogens containing arachidonic acid in the adipose tissue was markedly decreased. We also show by in vitro Elovl6 knockdown that the lipid network regulating the observed remodeling may be amenable to genetic modulation. Together, our novel approach suggests a physiological mechanism by which adaptation of adipocyte membranes to adipose tissue expansion associates with positive energy balance, potentially leading to higher vulnerability to inflammation in acquired obesity. Further studies will be needed to determine the cause of this effect.

  8. Effect of biophysical therapy on articular pain in a primary care setting compared to ibuprofen and placebo: a randomized controlled trial.

    Science.gov (United States)

    Foletti, A; Egan, C G; Baron, P

    2018-01-01

    Articular pain is one of the most frequent complaints practitioners face in their daily work. With an aging population, many patients have multiple comorbidities that are associated with the presence of chronic diseases, while others experience allergies, side effects or do not respond to standard medications or procedures. Therefore, there is an urgent need for new effective and safe strategies to manage articular pain, especially in its chronic manifestations. This randomized controlled trial was designed to assess the efficacy of a single therapy session using a biophysical procedure matched with a common non-steroidal anti-inflammatory drug (ibuprofen) and placebo. Biophysical therapy was performed using a Med Select 729 device. One hundred fifty patients (mean age 56±15.6 years) diagnosed with acute or chronic articular pain at different locations were randomized into 3 groups and the Numeric Pain Rating Score (NPRS) was used to measure pain at baseline, after one week, one month, and three months. While no difference in NPRS was observed at baseline among the 3 groups, a statistically significant difference was observed at all subsequent time points, respectively, after one week (p less than 0.05), one month (p less than 0.001), and three months (p less than 0.01), for both ibuprofen and biophysical groups vs placebo. Biophysical treatment of articular pain was shown to be as effective as a conventional non-steroidal anti-inflammatory treatment over a period of 3 months compared to placebo and could, therefore, represent an integrative, safe and long-lasting therapy to be considered for the management of acute and particularly chronic articular pain in current medical practice.

  9. Fundamentals of membrane bioreactors materials, systems and membrane fouling

    CERN Document Server

    Ladewig, Bradley

    2017-01-01

    This book provides a critical, carefully researched, up-to-date summary of membranes for membrane bioreactors. It presents a comprehensive and self-contained outline of the fundamentals of membrane bioreactors, especially their relevance as an advanced water treatment technology. This outline helps to bring the technology to the readers’ attention, and positions the critical topic of membrane fouling as one of the key impediments to its more widescale adoption. The target readership includes researchers and industrial practitioners with an interest in membrane bioreactors.

  10. Evaluation of changes in skin biophysical parameters and appearance after pneumatic injections of non-cross-linked hyaluronic acid in the face.

    Science.gov (United States)

    Cheng, Hai-Yan; Chen, Yu-Xin; Wang, Mei-Fang; Zhao, Jun-Ying; Li, Lin-Feng

    2018-03-15

    Pneumatic injections of non-cross-linked hyaluronic acid are effective in skin rejuvenation, however, the associated biophysical parameters and appearance have not been evaluated. To determine the changes in skin biophysical parameters after facial pneumatic injections of non-cross-linked hyaluronic acid. Twenty-eight healthy female volunteers received pneumatic injections of non-cross-linked hyaluronic acid into the face for consecutive 5 weeks. Skin biophysical parameter assessment and clinical evaluation were performed using the CK Multi-Probe Adapter and Visia system. Five of the volunteers also underwent retroauricular skin biopsy before and after the last treatment. The skin tissues were all stained with Masson-trichrome, Verhoeff-van Gieson stain, and hematoxylin-eosin to evaluate the changes in collagen, elastic fibers, and the epidermis, before and after the last treatment. Transepidermal water loss was significantly lower in week 4 (18.46 ± 4.70 g/h/m 2 ) than at the baseline (22.03 ± 7.15 g/h/m 2 , p pores also improved significantly at week 4 (934.07 ± 458.78) compared to the baseline (1024.57 ± 415.31, p pores, and wrinkles.

  11. Adaptive silicone-membrane lenses: planar vs. shaped membrane

    CSIR Research Space (South Africa)

    Schneider, F

    2009-08-01

    Full Text Available Engineering, Georges-Koehler-Allee 102, Freiburg 79110, Germany florian.schneider@imtek.uni-freiburg.de ABSTRACT We compare the performance and optical quality of two types of adaptive fluidic silicone-membrane lenses. The membranes feature either a...-membrane lenses: planar vs. shaped membrane Florian Schneider1,2, Philipp Waibel2 and Ulrike Wallrabe2 1 CSIR, Materials Science and Manufacturing, PO Box 395, Pretoria 0001, South Africa 2 University of Freiburg – IMTEK, Department of Microsystems...

  12. Degradation of Polypropylene Membranes Applied in Membrane Distillation Crystallizer

    Directory of Open Access Journals (Sweden)

    Marek Gryta

    2016-03-01

    Full Text Available The studies on the resistance to degradation of capillary polypropylene membranes assembled in a membrane crystallizer were performed. The supersaturation state of salt was achieved by evaporation of water from the NaCl saturated solutions using membrane distillation process. A high feed temperature (363 K was used in order to enhance the degradation effects and to shorten the test times. Salt crystallization was carried out by the application of batch or fluidized bed crystallizer. A significant membrane scaling was observed regardless of the method of realized crystallization. The SEM-EDS, DSC, and FTIR methods were used for investigations of polypropylene degradation. The salt crystallization onto the membrane surface accelerated polypropylene degradation. Due to a polymer degradation, the presence of carbonyl groups on the membranes’ surface was identified. Besides the changes in the chemical structure a significant mechanical damage of the membranes, mainly caused by the internal scaling, was also found. As a result, the membranes were severely damaged after 150 h of process operation. A high level of salt rejection was maintained despite damage to the external membrane surface.

  13. Biophysical Assessment of Single Cell Cytotoxicity: Diesel Exhaust Particle-Treated Human Aortic Endothelial Cells

    OpenAIRE

    Wu, Yangzhe; Yu, Tian; Gilbertson, Timothy A.; Zhou, Anhong; Xu, Hao; Nguyen, Kytai Truong

    2012-01-01

    Exposure to diesel exhaust particles (DEPs), a major source of traffic-related air pollution, has become a serious health concern due to its adverse influences on human health including cardiovascular and respiratory disorders. To elucidate the relationship between biophysical properties (cell topography, cytoskeleton organizations, and cell mechanics) and functions of endothelial cells exposed to DEPs, atomic force microscope (AFM) was applied to analyze the toxic effects of DEPs on a model ...

  14. Coexistence between silent and bursting states in a biophysical Hodgkin-Huxley-type of model

    DEFF Research Database (Denmark)

    Stankevich, Nataliya; Mosekilde, Erik

    2017-01-01

    in a slightly modified, biophysical model that describe the dynamics of pancreatic beta-cells. To realize this form of coexistence, we have introduced an additional voltage-dependent potassium current that is activated in the region around the original, unstable equilibrium point. It is interesting to note...... that this modification also leads the model to display a blue-sky catastrophe in the transition region between chaotic and bursting states....

  15. Membrane fusion

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    At Stanford University, Boxer lab, I worked on membrane fusion of small unilamellar lipid vesicles to flat membranes tethered to glass surfaces. This geometry closely resembles biological systems in which liposomes fuse to plasma membranes. The fusion mechanism was studied using DNA zippering...... between complementary strands linked to the two apposing membranes closely mimicking the zippering mechanism of SNARE fusion complexes....

  16. Introducing Membrane Charge and Membrane Potential to T Cell Signaling

    Directory of Open Access Journals (Sweden)

    Yuanqing Ma

    2017-11-01

    Full Text Available While membrane models now include the heterogeneous distribution of lipids, the impact of membrane charges on regulating the association of proteins with the plasma membrane is often overlooked. Charged lipids are asymmetrically distributed between the two leaflets of the plasma membrane, resulting in the inner leaflet being negatively charged and a surface potential that attracts and binds positively charged ions, proteins, and peptide motifs. These interactions not only create a transmembrane potential but they can also facilitate the formation of charged membrane domains. Here, we reference fields outside of immunology in which consequences of membrane charge are better characterized to highlight important mechanisms. We then focus on T cell receptor (TCR signaling, reviewing the evidence that membrane charges and membrane-associated calcium regulate phosphorylation of the TCR–CD3 complex and discuss how the immunological synapse exhibits distinct patterns of membrane charge distribution. We propose that charged lipids, ions in solution, and transient protein interactions form a dynamic equilibrium during T cell activation.

  17. Planning for sustainable tourism in southern Pulau Banggi: an assessment of biophysical conditions and their implications for future tourism development.

    Science.gov (United States)

    Teh, Lydia; Cabanban, Annadel S

    2007-12-01

    A priori assessments of a site's biophysical and socio-economic capacity for accommodating tourism are less common than tourism impact studies. A priori evaluations can provide a contextual understanding of ecological, economic and socio-cultural forces, which shape the prospects for sustainable tourism development at the host destination, and can avert adverse impacts of tourism. We conduct an a priori assessment of the biophysical environment of Pulau Banggi, in the Malaysian state of Sabah for sustainable tourism development. We characterise baseline conditions of the island's marine biodiversity, seasonality, and infrastructure. We then evaluate how existing biophysical conditions will influence options for sustainable tourism development. In particular, we suggest conditions, if there are any, which constitute a limit to future tourism development in terms of compatibility for recreation and resilience to visitor impacts. We find that the biggest constraint is the lack of adequate water and sanitation infrastructure. Blast fishing, although occurring less than once per hour, can potentially destroy the major attraction for tourists. We conclude that while Pulau Banggi possesses natural qualities that are attractive for ecotourism, financial and institutional support must be made available to provide facilities and services that will enable local participation in environmental protection and enhance prospects for future sustainable tourism.

  18. Polyazole hollow fiber membranes for direct contact membrane distillation

    KAUST Repository

    Maab, Husnul; Alsaadi, Ahmad Salem; Francis, Lijo; Livazovic, Sara; Ghaffour, NorEddine; Amy, Gary L.; Nunes, Suzana Pereira

    2013-01-01

    Porous hollow fiber membranes were fabricated from fluorinated polyoxadiazole and polytriazole by a dry-wet spinning method for application in desalination of Red Sea water by direct contact membrane distillation (DCMD). The data were compared with commercially available hollow fiber MD membranes prepared from poly(vinylidene fluoride). The membranes were characterized by electron microscopy, liquid entry pressure (LEP), and pore diameter measurements. Finally, the hollow fiber membranes were tested for DCMD. Salt selectivity as high as 99.95% and water fluxes as high as 35 and 41 L m -2 h-1 were demonstrated, respectively, for polyoxadiazole and polytriazole hollow fiber membranes, operating at 80 C feed temperature and 20 C permeate. © 2013 American Chemical Society.

  19. Polyazole hollow fiber membranes for direct contact membrane distillation

    KAUST Repository

    Maab, Husnul

    2013-08-07

    Porous hollow fiber membranes were fabricated from fluorinated polyoxadiazole and polytriazole by a dry-wet spinning method for application in desalination of Red Sea water by direct contact membrane distillation (DCMD). The data were compared with commercially available hollow fiber MD membranes prepared from poly(vinylidene fluoride). The membranes were characterized by electron microscopy, liquid entry pressure (LEP), and pore diameter measurements. Finally, the hollow fiber membranes were tested for DCMD. Salt selectivity as high as 99.95% and water fluxes as high as 35 and 41 L m -2 h-1 were demonstrated, respectively, for polyoxadiazole and polytriazole hollow fiber membranes, operating at 80 C feed temperature and 20 C permeate. © 2013 American Chemical Society.

  20. Simulation of Tillage Systems Impact on Soil Biophysical Properties Using the SALUS Model

    Directory of Open Access Journals (Sweden)

    Luigi Sartori

    2011-02-01

    Full Text Available A sustainable land management has been defined as the management system that allows for production, while minimizing risk, maintaining quality of soil and water. Tillage systems can significantly decrease soil carbon storage and influence the soil environment of a crop. Crop growth models can be useful tools in evaluating the impact of different tillage systems on soil biophysical properties and on the growth and final yield of the crops. The objectives of this paper were i to illustrate the SALUS model and its tillage component; ii to evaluate the effects of different tillage systems on water infiltration and time to ponding, iii to simulate the effect of tillage systems on some soil biophysical properties. The SALUS (System Approach to Land Use Sustainability model is designed to simulate continuous crop, soil, water and nutrient conditions under different tillage and crop residues management strategies for multiple years. Predictions of changes in surface residue, bulk density, runoff, drainage and evaporation were consistent with expected behaviours of these parameters as described in the literature. The experiment to estimate the time to ponding curve under different tillage system confirmed the theory and showed the beneficial effects of the residue on soil surface with respect to water infiltration. It also showed that the no-tillage system is a more appropriate system to adopt in areas characterized by high intensity rainfall.