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Sample records for f1-atpase molecular motor

  1. The nonlinear chemo-mechanic coupled dynamics of the F 1 -ATPase molecular motor.

    Science.gov (United States)

    Xu, Lizhong; Liu, Fang

    2012-03-01

    The ATP synthase consists of two opposing rotary motors, F0 and F1, coupled to each other. When the F1 motor is not coupled to the F0 motor, it can work in the direction hydrolyzing ATP, as a nanomotor called F1-ATPase. It has been reported that the stiffness of the protein varies nonlinearly with increasing load. The nonlinearity has an important effect on the rotating rate of the F1-ATPase. Here, considering the nonlinearity of the γ shaft stiffness for the F1-ATPase, a nonlinear chemo-mechanical coupled dynamic model of F1 motor is proposed. Nonlinear vibration frequencies of the γ shaft and their changes along with the system parameters are investigated. The nonlinear stochastic response of the elastic γ shaft to thermal excitation is analyzed. The results show that the stiffness nonlinearity of the γ shaft causes an increase of the vibration frequency for the F1 motor, which increases the motor's rotation rate. When the concentration of ATP is relatively high and the load torque is small, the effects of the stiffness nonlinearity on the rotating rates of the F1 motor are obvious and should be considered. These results are useful for improving calculation of the rotating rate for the F1 motor and provide insight about the stochastic wave mechanics of F1-ATPase.

  2. Torque, chemistry and efficiency in molecular motors: a study of the rotary-chemical coupling in F1-ATPase.

    Science.gov (United States)

    Mukherjee, Shayantani; Bora, Ram Prasad; Warshel, Arieh

    2015-11-01

    Detailed understanding of the action of biological molecular machines must overcome the challenge of gaining a clear knowledge of the corresponding free-energy landscape. An example for this is the elucidation of the nature of converting chemical energy to torque and work in the rotary molecular motor of F1-ATPase. A major part of the challenge involves understanding the rotary-chemical coupling from a non-phenomenological structure/energy description. Here we focused on using a coarse-grained model of F1-ATPase to generate a structure-based free-energy landscape of the rotary-chemical process of the whole system. In particular, we concentrated on exploring the possible impact of the position of the catalytic dwell on the efficiency and torque generation of the molecular machine. It was found that the experimentally observed torque can be reproduced with landscapes that have different positions for the catalytic dwell on the rotary-chemical surface. Thus, although the catalysis is undeniably required for torque generation, the experimentally observed position of the catalytic dwell at 80° might not have a clear advantage for the force generation by F1-ATPase. This further implies that the rotary-chemical couplings in these biological motors are quite robust and their efficiencies do not depend explicitly on the position of the catalytic dwells. Rather, the specific positioning of the dwells with respect to the rotational angle is a characteristic arising due to the structural construct of the molecular machine and might not bear any clear connection to the thermodynamic efficiency for the system.

  3. Single molecule energetics of F1-ATPase motor.

    Science.gov (United States)

    Muneyuki, Eiro; Watanabe-Nakayama, Takahiro; Suzuki, Tetsuya; Yoshida, Masasuke; Nishizaka, Takayuki; Noji, Hiroyuki

    2007-03-01

    Motor proteins are essential in life processes because they convert the free energy of ATP hydrolysis to mechanical work. However, the fundamental question on how they work when different amounts of free energy are released after ATP hydrolysis remains unanswered. To answer this question, it is essential to clarify how the stepping motion of a motor protein reflects the concentrations of ATP, ADP, and P(i) in its individual actions at a single molecule level. The F(1) portion of ATP synthase, also called F(1)-ATPase, is a rotary molecular motor in which the central gamma-subunit rotates against the alpha(3)beta(3) cylinder. The motor exhibits clear step motion at low ATP concentrations. The rotary action of this motor is processive and generates a high torque. These features are ideal for exploring the relationship between free energy input and mechanical work output, but there is a serious problem in that this motor is severely inhibited by ADP. In this study, we overcame this problem of ADP inhibition by introducing several mutations while retaining high enzymatic activity. Using a probe of attached beads, stepping rotation against viscous load was examined at a wide range of free energy values by changing the ADP concentration. The results showed that the apparent work of each individual step motion was not affected by the free energy of ATP hydrolysis, but the frequency of each individual step motion depended on the free energy. This is the first study that examined the stepping motion of a molecular motor at a single molecule level with simultaneous systematic control of DeltaG(ATP). The results imply that microscopically defined work at a single molecule level cannot be directly compared with macroscopically defined free energy input.

  4. Simple mechanism whereby the F1-ATPase motor rotates with near-perfect chemomechanical energy conversion.

    Science.gov (United States)

    Saita, Ei-ichiro; Suzuki, Toshiharu; Kinosita, Kazuhiko; Yoshida, Masasuke

    2015-08-04

    F1-ATPase is a motor enzyme in which a central shaft γ subunit rotates 120° per ATP in the cylinder made of α3β3 subunits. During rotation, the chemical energy of ATP hydrolysis (ΔGATP) is converted almost entirely into mechanical work by an elusive mechanism. We measured the force for rotation (torque) under various ΔGATP conditions as a function of rotation angles of the γ subunit with quasi-static, single-molecule manipulation and estimated mechanical work (torque × traveled angle) from the area of the function. The torque functions show three sawtooth-like repeats of a steep jump and linear descent in one catalytic turnover, indicating a simple physical model in which the motor is driven by three springs aligned along a 120° rotation angle. Although the second spring is unaffected by ΔGATP, activation of the first spring (timing of the torque jump) delays at low [ATP] (or high [ADP]) and activation of the third spring delays at high [Pi]. These shifts decrease the size and area of the sawtooth (magnitude of the work). Thus, F1-ATPase responds to the change of ΔGATP by shifting the torque jump timing and uses ΔGATP for the mechanical work with near-perfect efficiency.

  5. Trypanosoma brucei TbIF1 inhibits the essential F1-ATPase in the infectious form of the parasite.

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    Brian Panicucci

    2017-04-01

    Full Text Available The mitochondrial (mt FoF1-ATP synthase of the digenetic parasite, Trypanosoma brucei, generates ATP during the insect procyclic form (PF, but becomes a perpetual consumer of ATP in the mammalian bloodstream form (BF, which lacks a canonical respiratory chain. This unconventional dependence on FoF1-ATPase is required to maintain the essential mt membrane potential (Δψm. Normally, ATP hydrolysis by this rotary molecular motor is restricted to when eukaryotic cells experience sporadic hypoxic conditions, during which this compulsory function quickly depletes the cellular ATP pool. To protect against this cellular treason, the highly conserved inhibitory factor 1 (IF1 binds the enzyme in a manner that solely inhibits the hydrolytic activity. Intriguingly, we were able to identify the IF1 homolog in T. brucei (TbIF1, but determined that its expression in the mitochondrion is tightly regulated throughout the life cycle as it is only detected in PF cells. TbIF1 appears to primarily function as an emergency brake in PF cells, where it prevented the restoration of the Δψm by FoF1-ATPase when respiration was chemically inhibited. In vitro, TbIF1 overexpression specifically inhibits the hydrolytic activity but not the synthetic capability of the FoF1-ATP synthase in PF mitochondria. Furthermore, low μM amounts of recombinant TbIF1 achieve the same inhibition of total mt ATPase activity as the FoF1-ATPase specific inhibitors, azide and oligomycin. Therefore, even minimal ectopic expression of TbIF1 in BF cells proved lethal as the indispensable Δψm collapsed due to inhibited FoF1-ATPase. In summary, we provide evidence that T. brucei harbors a natural and potent unidirectional inhibitor of the vital FoF1-ATPase activity that can be exploited for future structure-based drug design.

  6. Recovery of state-specific potential of molecular motor from single-molecule trajectory

    CERN Document Server

    Toyabe, Shoichi; Muneyuki, Eiro

    2011-01-01

    We have developed a novel method to evaluate the potential profile of a molecular motor at each chemical state from only the probe's trajectory and applied it to a rotary molecular motor F$_1$-ATPase. By using this method, we could also obtain the information regarding the mechanochemical coupling and energetics. We demonstrate that the position-dependent transition of the chemical states is the key feature for the highly efficient free-energy transduction by F$_1$-ATPase.

  7. Robustness of the rotary catalysis mechanism of F1-ATPase.

    Science.gov (United States)

    Watanabe, Rikiya; Matsukage, Yuki; Yukawa, Ayako; Tabata, Kazuhito V; Noji, Hiroyuki

    2014-07-11

    F1-ATPase (F1) is the rotary motor protein fueled by ATP hydrolysis. Previous studies have suggested that three charged residues are indispensable for catalysis of F1 as follows: the P-loop lysine in the phosphate-binding loop, GXXXXGK(T/S); a glutamic acid that activates water molecules for nucleophilic attack on the γ-phosphate of ATP (general base); and an arginine directly contacting the γ-phosphate (arginine finger). These residues are well conserved among P-loop NTPases. In this study, we investigated the role of these charged residues in catalysis and torque generation by analyzing alanine-substituted mutants in the single-molecule rotation assay. Surprisingly, all mutants continuously drove rotary motion, even though the rotational velocity was at least 100,000 times slower than that of wild type. Thus, although these charged residues contribute to highly efficient catalysis, they are not indispensable to chemo-mechanical energy coupling, and the rotary catalysis mechanism of F1 is far more robust than previously thought.

  8. Operating principles of rotary molecular motors: differences between F1 and V1 motors.

    Science.gov (United States)

    Yamato, Ichiro; Kakinuma, Yoshimi; Murata, Takeshi

    2016-01-01

    Among the many types of bioenergy-transducing machineries, F- and V-ATPases are unique bio- and nano-molecular rotary motors. The rotational catalysis of F1-ATPase has been investigated in detail, and molecular mechanisms have been proposed based on the crystal structures of the complex and on extensive single-molecule rotational observations. Recently, we obtained crystal structures of bacterial V1-ATPase (A3B3 and A3B3DF complexes) in the presence and absence of nucleotides. Based on these new structures, we present a novel model for the rotational catalysis mechanism of V1-ATPase, which is different from that of F1-ATPases.

  9. Oxidative phosphorylation in Escherichia coli. Characterization of mutant strains in which F1-ATPase contains abnormal beta-subunits.

    Science.gov (United States)

    Senior, A E; Langman, L; Cox, G B; Gibson, F

    1983-02-15

    To facilitate study of the role of the beta-subunit in the membrane-bound proton-translocating ATPase of Escherichia coli, we identified mutant strains from which an F1-ATPase containing abnormal beta-subunits can be purified. Seventeen strains of E. coli, characterized by genetic complementation tests as carrying mutations in the uncD gene (which codes for the beta-subunit), were studied. The majority of these strains (11) were judged to be not useful, as their membranes lacked ATPase activity, and were either proton-permeable as prepared or remained proton-impermeable after washing with buffer of low ionic strength. A further two strains were of a type not hitherto reported, in that their membranes had ATPase activity, were proton-impermeable as prepared, and were not rendered proton-permeable by washing in buffer of low ionic strength. Presumably in these two strains F1-ATPase is not released in soluble form by this procedure. F1-ATPase of normal molecular size were purified from strains AN1340 (uncD478), AN937 (uncD430), AN938 (uncD431) and AN1543 (uncD484). F1-ATPase from strain AN1340 (uncD478) had 15% of normal specific Mg-dependent ATPase activity and 22% of normal ATP-synthesis activity. The F1-ATPase preparations from strains AN937, AN938 and AN1543 had respectively 1.7%, 1.8% and 0.2% of normal specific Mg-dependent ATPase activity, and each of these preparations had very low ATP-synthesis activity. The yield of F1-ATPase from the four strains described was almost twice that obtained from a normal haploid strain. The kinetics of Ca-dependent ATPase activity were unusual in each of the four F1-ATPase preparations. It is likely that these four mutant uncD F1-ATPase preparations will prove valuable for further experimental study of the F1-ATPase catalytic mechanism.

  10. None of the Rotor Residues of F1-ATPase Are Essential for Torque Generation

    Science.gov (United States)

    Chiwata, Ryohei; Kohori, Ayako; Kawakami, Tomonari; Shiroguchi, Katsuyuki; Furuike, Shou; Adachi, Kengo; Sutoh, Kazuo; Yoshida, Masasuke; Kinosita, Kazuhiko

    2014-01-01

    F1-ATPase is a powerful rotary molecular motor that can rotate an object several hundred times as large as the motor itself against the viscous friction of water. Forced reverse rotation has been shown to lead to ATP synthesis, implying that the mechanical work against the motor’s high torque can be converted into the chemical energy of ATP. The minimal composition of the motor protein is α3β3γ subunits, where the central rotor subunit γ turns inside a stator cylinder made of alternately arranged α3β3 subunits using the energy derived from ATP hydrolysis. The rotor consists of an axle, a coiled coil of the amino- and carboxyl-terminal α-helices of γ, which deeply penetrates the stator cylinder, and a globular protrusion that juts out from the stator. Previous work has shown that, for a thermophilic F1, significant portions of the axle can be truncated and the motor still rotates a submicron sized bead duplex, indicating generation of up to half the wild-type (WT) torque. Here, we inquire if any specific interactions between the stator and the rest of the rotor are needed for the generation of a sizable torque. We truncated the protruding portion of the rotor and replaced part of the remaining axle residues such that every residue of the rotor has been deleted or replaced in this or previous truncation mutants. This protrusionless construct showed an unloaded rotary speed about a quarter of the WT, and generated one-third to one-half of the WT torque. No residue-specific interactions are needed for this much performance. F1 is so designed that the basic rotor-stator interactions for torque generation and control of catalysis rely solely upon the shape and size of the rotor at very low resolution. Additional tailored interactions augment the torque to allow ATP synthesis under physiological conditions. PMID:24853745

  11. Regulation of the thermoalkaliphilic F1-ATPase from Caldalkalibacillus thermarum

    Science.gov (United States)

    Ferguson, Scott A.; Cook, Gregory M.; Montgomery, Martin G.; Leslie, Andrew G. W.

    2016-01-01

    The crystal structure has been determined of the F1-catalytic domain of the F-ATPase from Caldalkalibacillus thermarum, which hydrolyzes adenosine triphosphate (ATP) poorly. It is very similar to those of active mitochondrial and bacterial F1-ATPases. In the F-ATPase from Geobacillus stearothermophilus, conformational changes in the ε-subunit are influenced by intracellular ATP concentration and membrane potential. When ATP is plentiful, the ε-subunit assumes a “down” state, with an ATP molecule bound to its two C-terminal α-helices; when ATP is scarce, the α-helices are proposed to inhibit ATP hydrolysis by assuming an “up” state, where the α-helices, devoid of ATP, enter the α3β3-catalytic region. However, in the Escherichia coli enzyme, there is no evidence that such ATP binding to the ε-subunit is mechanistically important for modulating the enzyme’s hydrolytic activity. In the structure of the F1-ATPase from C. thermarum, ATP and a magnesium ion are bound to the α-helices in the down state. In a form with a mutated ε-subunit unable to bind ATP, the enzyme remains inactive and the ε-subunit is down. Therefore, neither the γ-subunit nor the regulatory ATP bound to the ε-subunit is involved in the inhibitory mechanism of this particular enzyme. The structure of the α3β3-catalytic domain is likewise closely similar to those of active F1-ATPases. However, although the βE-catalytic site is in the usual “open” conformation, it is occupied by the unique combination of an ADP molecule with no magnesium ion and a phosphate ion. These bound hydrolytic products are likely to be the basis of inhibition of ATP hydrolysis. PMID:27621435

  12. Mg2+ coordination in catalytic sites of F1-ATPase.

    Science.gov (United States)

    Weber, J; Hammond, S T; Wilke-Mounts, S; Senior, A E

    1998-01-13

    Coordination of the Mg2+ ion in Mg-nucleotide substrates by amino acid residue side chains in the catalytic site of Escherichia coli F1-ATPase was investigated. From the X-ray structure of the mitochondrial enzyme [Abrahams, J. P., Leslie, A. G. W., Lutter, R., and Walker, J. E. (1994) Nature 370, 621-628], it may be inferred that the hydroxyl of betaThr-156 is a direct ligand of Mg2+, whereas the carboxyls of betaGlu-181, betaGlu-185, and betaAsp-242 might contribute via intervening water molecules. Elimination of each respective functional group by site-directed mutagenesis, followed by determination of Mg-nucleotide and uncomplexed nucleotide binding affinities using a tryptophan probe, showed that betaThr-156, betaGlu-185, and betaAsp-242 are all involved in Mg2+ coordination, whereas betaGlu-181 is not. A derived structural model for the octahedral coordination around the Mg2+ ion is presented. The results indicate that the ADP-containing site in the X-ray structure is the catalytic site of highest affinity. Correct Mg2+ coordination is required for catalytic activity at physiological rates. Elimination of any one of the Mg2+-coordinating residues led to complete loss of Mg2+-dependent nucleotide binding cooperativity of the catalytic sites.

  13. Highly sensitive detection of NT-proBNP by molecular motor

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    Jie Zhang

    2017-03-01

    Full Text Available FoF1-ATPase is an active rotary motor, and generates three-ATP for each rotation. At saturated substrate concentration, the motor can achieve about 103 r.p.m, which means one motor can generate about 105 ATP molecules during 30 min. Here, we constituted a novel nanodevice with a molecular rotary motor and a “battery”, FoF1-ATPase and chromatophore, and presented a novel method of sandwich type rotary biosensor based on ε subunit with one target-to-one motor, in which one target corresponds 105 ATP molecules as detection signals during 30 min. The target such as NT-proBNP detection demonstrated that this novel nanodevice has potential to be developed into an ultrasensitive biosensor to detect low expressed targets.

  14. Surface Plasmon Resonance Analysis of Histidine-Tagged F1-ATPase Surface Adsorption

    Science.gov (United States)

    Tucker, Jenifer K.; Richter, Mark L.; Berrie, Cindy L.

    2015-11-01

    Studies of the rotational activity of the enzymatic core (α3β3γ) of the F1-ATPase motor protein have relied on binding the enzyme to NTA-coated glass surfaces via polyhistidine tags engineered into the C-termini of each of the three α or β subunits. Those studies revealed the rotational motion of the central γ subunit by monitoring the motion of attached micron-long actin filaments or spherical nanoparticles. However, only a small percentage of the attached filaments or particles were observed to rotate, likely due, at least in part, to non-uniform surface attachment of the motor proteins. In this study, we have applied surface plasmon resonance to monitor the kinetics and affinity of binding of the His-tagged motor protein to NTA-coated gold sensor surfaces. The binding data, when fit to a heterogeneous binding model, exhibit two sets of adsorption-desorption rate constants with two dissociation constants of 4.0 × 10-9 M and 8.6 × 10-11 M for 6His-α3β3γ binding to the nickel ion-activated NTA surface. The data are consistent with mixed attachment of the protein via two (bimodal) and three (trimodal) NTA/Ni2+-His-tag interactions, respectively, with the less stable bimodal interaction dominating. The results provide a partial explanation for the low number of surface-attached F1 motors previously observed in rotation studies and suggest alternative approaches to uniform F1 motor surface attachment for future fabrication of motor-based nanobiodevices and materials.

  15. High-Pressure Microscopy for Studying Molecular Motors.

    Science.gov (United States)

    Nishiyama, Masayoshi

    2015-01-01

    Movement is a fundamental characteristic of all living things. This biogenic function is carried out by various nanometer-sized molecular machines. Molecular motor is a typical molecular machinery in which the characteristic features of proteins are integrated; these include enzymatic activity, energy conversion, molecular recognition and self-assembly. These biologically important reactions occur with the association of water molecules that surround the motors. Applied pressures can alter the intermolecular interactions between the motors and water. In this chapter we describe the development of a high-pressure microscope and a new motility assay that enables the visualization of the motility of molecular motors under conditions of high-pressure. Our results demonstrate that applied pressure dynamically changes the motility of molecular motors such as kinesin, F1-ATPase and bacterial flagellar motors.

  16. Effects of an ATP analogue, adenosine 5'-[α-thio]-triphosphate, on F1-ATPase rotary catalysis, torque generation, and inhibited intermediated formation.

    Science.gov (United States)

    Yukawa, Ayako; Watanabe, Rikiya; Noji, Hiroyuki

    2015-03-13

    F1-ATPase (F1), an important rotary motor protein, converts the chemical energy of ATP hydrolysis into mechanical energy using rotary motion with extremely high efficiency. The energy-conversion mechanism for this molecular motor has been extensively clarified by previous studies, which indicate that the interactions between the catalytic residues and the β- and γ-phosphates of ATP are indispensable for efficient catalysis and torque generation. However, the role of α-phosphate is largely unknown. In this study, we observed the rotation of F1 fuelled with an ATP analogue, adenosine 5'-[α-thio]-triphosphate (ATPαS), in which the oxygen has been substituted with a sulfur ion to perturb the α-phosphate/F1 interactions. In doing so, we have revealed that ATPαS does not appear to have any impact on the kinetic properties of the motor or on torque generation compared to ATP. On the other hand, F1 was observed to lapse into the ADP-inhibited intermediate states when in the presence of ATPαS more severely than in the presence of ATP, suggesting that the α-phosphate group of ATP contributes to the avoidance of ADP-inhibited intermediate formation.

  17. Properties of F1-ATPase from the uncD412 mutant of Escherichia coli.

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    Wise, J G; Duncan, T M; Latchney, L R; Cox, D N; Senior, A E

    1983-11-01

    Properties of purified F1-ATPase from Escherichia coli mutant strain AN484 (uncD412) have been studied in an attempt to understand why the amino acid substitution in the beta-subunit of this enzyme causes a tenfold reduction from normal MgATP hydrolysis rate. In most properties that were studied, uncD412 F1-ATPase resembled normal E. coli F1-ATPase. Both enzymes were found to contain a total of six adenine-nucleotide-binding sites, of which three were found to be non-exchangeable and three were exchangeable (catalytic) sites. Binding of the non-hydrolysable substrate analogue adenosine 5'-[beta gamma-imido]triphosphate (p[NH]ppA) to the three exchangeable sites showed apparent negative co-operativity. The binding affinities for p[NH]ppA, and also ADP, at the exchangeable sites were similar in the two enzymes. Both enzymes were inhibited by efrapeptin, aurovertin and p[NH]ppA, and were inactivated by dicyclohexylcarbodi-imide, 4-chloro-7-nitrobenzofurazan and p-fluorosulphonyl-benzoyl-5'-adenosine. Km values for CaATP and MgATP were similar in the two enzymes. uncD412 F1-ATPase was abnormally unstable at high pH, and dissociated into subunits readily with consequent loss of activity. The reason for the impairment of catalysis in uncD412 F1-ATPase cannot be stated with certainty from these studies. However we discuss the possibility that the mutation interrupts subunit interaction, thereby causing a partial impairment in the site-site co-operativity which is required for 'promotion' of catalysis in this enzyme.

  18. How molecular motors work - insights from the molecular machinist's toolbox: the Nobel prize in Chemistry 2016.

    Science.gov (United States)

    Astumian, R D

    2017-02-01

    The Nobel prize in Chemistry for 2016 was awarded to Jean Pierre Sauvage, Sir James Fraser Stoddart, and Bernard (Ben) Feringa for their contributions to the design and synthesis of molecular machines. While this field is still in its infancy, and at present there are no commercial applications, many observers have stressed the tremendous potential of molecular machines to revolutionize technology. However, perhaps the most important result so far accruing from the synthesis of molecular machines is the insight provided into the fundamental mechanisms by which molecular motors, including biological motors such as kinesin, myosin, FoF1 ATPase, and the flagellar motor, function. The ability to "tinker" with separate components of molecular motors allows asking, and answering, specific questions about mechanism, particularly with regard to light driven vs. chemistry driven molecular motors.

  19. Enhanced Diffusion of Molecular Motors in the Presence of Adenosine Triphosphate and External Force

    Science.gov (United States)

    Shinagawa, Ryota; Sasaki, Kazuo

    2016-06-01

    The diffusion of a molecular motor in the presence of a constant external force is considered on the basis of a simple theoretical model. The motor is represented by a Brownian particle moving in a series of parabolic potentials placed periodically on a line, and the potential is switched stochastically from one parabola to another by a chemical reaction, which corresponds to the hydrolysis or synthesis of adenosine triphosphate (ATP) in motor proteins. It is found that the diffusion coefficient as a function of the force exhibits peaks. The mechanism of this diffusion enhancement and the possibility of observing it in F1-ATPase, a biological rotary motor, are discussed.

  20. Quaternary structure of V1 and F1 ATPase: significance of structural homologies and diversities.

    Science.gov (United States)

    Svergun, D I; Konrad, S; Huss, M; Koch, M H; Wieczorek, H; Altendorf, K; Volkov, V V; Grüber, G

    1998-12-22

    The V1 ATPase from the tobacco hornworm Manduca sexta and the Escherichia coli F1 ATPase were characterized by small-angle X-ray scattering (SAXS). The radii of gyration (Rg) of the complexes were 6.2 +/- 0.1 and 4.7 +/- 0.02 nm, respectively. The shape of the M. sexta V1 ATPase was determined ab initio from the scattering data showing six masses, presumed to be the A and B subunits, arranged in an alternating manner about a 3-fold axis. A seventh mass with a length of about 11.0 nm extends perpendicularly to the center of the hexameric unit. This central mass is presumed to be the stalk that connects V1 with the membrane domain (V(O)) in the intact V1V(O)-ATPase. In comparison, the shape of the F1 ATPase from E. coli possesses a quasi-3-fold symmetry over the major part of the enzyme. The overall asymmetry of the structure is given by a stem, assumed to include the central stalk subunits. The features of the V1 and F1 ATPase reveal structural homologies and diversities of the key components of the complexes.

  1. Nanosized free-energy transducer F1-ATPase achieves 100% efficiency at finite time operation

    CERN Document Server

    Toyabe, Shoichi

    2012-01-01

    The free-energy transduction at 100% efficiency is not prohibited by thermodynamic laws. However, it is usually reached only at the quasi-static limit such as the macroscopic piston pulled or pushed at the infinitely slow velocity. If we operate the piston quickly, turbulence is inevitable and irreversible heat dissipates through the microscopic degrees of freedom. Here, we evaluated the work performed by the nano-sized biological free-energy transducer F1-ATPase by single-molecule experiments on the basis of nonequilibrium theory. We show that the F1-ATPase achieves a nearly 100% free-energy conversion efficiency even far from quasistatic process for both the mechanical-to-chemical and chemical-to-mechanical transductions. Such a high efficiency at a finite-time operation is not expected for macroscopic engines and highlights a remarkable property of the nano-sized engines working in the energy scale of k_{B}T. Some of the microscopic degrees of freedom may not be hidden but accessible to the F1-ATPase. Henc...

  2. Activation and inhibition of the Escherichia coli F1-ATPase by monoclonal antibodies which recognize the epsilon subunit.

    Science.gov (United States)

    Dunn, S D; Tozer, R G

    1987-02-15

    The properties of two monoclonal antibodies which recognize the epsilon subunit of Escherichia coli F1-ATPase were studied in detail. The epsilon subunit is a tightly bound but dissociable inhibitor of the ATPase activity of soluble F1-ATPase. Antibody epsilon-1 binds free epsilon with a dissociation constant of 2.4 nM but cannot bind epsilon when it is associated with F1-ATPase. Likewise epsilon cannot associate with F1-ATPase in the presence of high concentrations of epsilon-1. Thus epsilon-1 activates F1-ATPase which contains the epsilon subunit, and prevents added epsilon from inhibiting the enzyme. Epsilon-1 cannot bind to membrane-bound F1-ATPase. The epsilon-4 antibody binds free epsilon with a dissociation constant of 26 nM. Epsilon-4 can bind to the F1-ATPase complex, but, like epsilon-1, it reverses the inhibition of F1-ATPase by the epsilon subunit. The epsilon subunit remains crosslinkable to both the beta and gamma subunits in the presence of epsilon-4, indicating that it is not grossly displaced from its normal position by the antibody. Presumably the activation arises from more subtle conformational effects. Antibodies epsilon-4 and delta-2, which recognizes the delta subunit, both bind to F1F0 in E. coli membrane vesicles, indicating that these subunits are substantially exposed in the membrane-bound complex. Epsilon-4 inhibits the ATPase activity of the membrane-bound enzyme by about 50%, and Fab prepared from epsilon-4 inhibits by about 40%. This inhibition is not associated with any substantial change in the major apparent Km for ATP. These results suggest that inhibition of membrane-bound F1-ATPase arises from steric effects of the antibody.

  3. Recombinant bovine heart mitochondrial F1-ATPase inhibitor protein: overproduction in Escherichia coli, purification, and structural studies.

    Science.gov (United States)

    Van Heeke, G; Deforce, L; Schnizer, R A; Shaw, R; Couton, J M; Shaw, G; Song, P S; Schuster, S M

    1993-09-28

    A synthetic gene coding for the inhibitor protein of bovine heart mitochondrial F1 adenosine triphosphatase was designed and cloned in Escherichia coli. Recombinant F1-ATPase inhibitor protein was overproduced in E. coli and secreted to the periplasmic space. Biologically active recombinant F1-ATPase inhibitor protein was recovered from the bacterial cells by osmotic shock and was purified to near homogeneity in a single cation-exchange chromatography step. The recombinant inhibitor protein was shown to inhibit bovine mitochondrial F1-ATPase in a pH-dependent manner, as well as Saccharomyces cerevisiae mitochondrial F1-ATPase. Thorough analysis of the amino acid sequence revealed a potential coiled-coil structure for the C-terminal portion of the protein. Experimental evidence obtained by circular dichroism analyses supports this prediction and suggests F1I to be a highly stable, mainly alpha-helical protein which displays C-terminal alpha-helical coiled-coil intermolecular interaction.

  4. Binding and hydrolysis of TNP-ATP by Escherichia coli F1-ATPase.

    Science.gov (United States)

    Weber, J; Senior, A E

    1996-02-16

    It had previously been suggested that Vmax hydrolysis rate of 2', 3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP) by F1-ATPase required filling of only two catalytic sites on the enzyme (Grubmeyer, C., and Penefsky, H. S. (1981) J. Biol. Chem. 256, 3718-3727), whereas recently it was shown that Vmax rate of ATP hydrolysis requires that all three catalytic sites are filled (Weber, J., Wilke-Mounts, S., Lee, R. S. F., Grell, E., and Senior, A. E. (1993) J. Biol. Chem. 268, 20126-20133). To resolve this apparent discrepancy, we measured equilibrium binding and hydrolysis of MgTNP-ATP under identical conditions, using betaY331W mutant Escherichia coli F1-ATPase, in which the genetically engineered tryptophan provides a direct fluorescent probe of catalytic site occupancy. We found that MgTNP-ATP hydrolysis at Vmax rate did require filling of all three catalytic sites, but in contrast to the situation with MgATP, "bisite hydrolysis" of MgTNP-ATP amounted to a substantial fraction (approximately 40%) of Vmax. Binding of MgTNP-ATP to the three catalytic sites showed strong binding cooperativity (Kd1 e. in presence of EDTA) bound to all three catalytic sites with lower affinity but was not hydrolyzed. These data emphasize that the presence of Mg2+ is critical for cooperativity of substrate binding, formation of the very high affinity first catalytic site, and hydrolytic activity in F1-ATPases and that these three properties are strongly correlated.

  5. Engineering a light-controlled F1 ATPase using structure-based protein design

    OpenAIRE

    2016-01-01

    The F1 sub-complex of ATP synthase is a biological nanomotor that converts the free energy of ATP hydrolysis into mechanical work with an astonishing efficiency of up to 100% (Kinosita et al., 2000). To probe the principal mechanics of the machine, I re-engineered the active site of E.coli F1 ATPase with a structure-based protein design approach: by incorporation of a site-specific, photoswitchable crosslinker, whose end-to-end distance can be modulated by illumination with light of two diffe...

  6. E. coli F1-ATPase: site-directed mutagenesis of the beta-subunit.

    Science.gov (United States)

    Parsonage, D; Wilke-Mounts, S; Senior, A E

    1988-05-09

    Residues beta Glu-181 and beta Glu-192 of E. coli F1-ATPase (the DCCD-reactive residues) were mutated to Gln. Purified beta Gln-181 F1 showed 7-fold impairment of 'unisite' Pi formation from ATP and a large decrease in affinity for ATP. Thus the beta-181 carboxyl group in normal F1 significantly contributes to catalytic site properties. Also, positive catalytic site cooperativity was attenuated from 5 X 10(4)- to 548-fold in beta Gln-181 F1. In contrast, purified beta Gln-192 F1 showed only 6-fold reduction in 'multisite' ATPase activity. Residues beta Gly-149 and beta Gly-154 were mutated to Ile singly and in combination. These mutations, affecting residues which are strongly conserved in nucleotide-binding proteins, were chosen to hinder conformational motion in a putative 'flexible loop' in beta-subunit. Impairment of purified F1-ATPase ranged from 5 to 61%, with the double mutant F1 less impaired than either single mutant. F1 preparations containing beta Ile-154 showed 2-fold activation after release from membranes, suggesting association with F0 restrained turnover on F1 in these mutants.

  7. Nucleotide occupancy of F1-ATPase catalytic sites under crystallization conditions.

    Science.gov (United States)

    Löbau, S; Weber, J; Senior, A E

    1997-03-03

    Using site-directed tryptophan fluorescence we studied nucleotide occupancy of the catalytic sites of Escherichia coli F1-ATPase, under conditions used previously for crystallization and X-ray structure analysis of the bovine mitochondrial enzyme [Abrahams et al. (1994) Nature 370, 621-628]. We found that only two of the three catalytic sites were filled in the E. coli enzyme under these conditions (250 microM MgAMPPNP plus 5 microM MgADP), consistent with what was reported in the bovine F1 X-ray structure. However, subsequent addition of a physiological concentration of MgATP readily filled the third catalytic site. Therefore the enzyme form seen in the X-ray structure results from the fact that it is obtained under sub-saturating nucleotide conditions. The data show that the X-ray structure is compatible with a catalytic mechanism in which all three F1-ATPase catalytic sites must fill with MgATP to initiate steady-state hydrolysis [e.g. Weber and Senior (1996) Biochim. Biophys. Acta 1275, 101-104]. The data further demonstrate that the site-directed tryptophan fluorescence technique can provide valuable support for F1 crystallography studies.

  8. Solution structure and function in trifluoroethanol of PP-50, an ATP-binding peptide from F1ATPase.

    Science.gov (United States)

    Chuang, W J; Abeygunawardana, C; Gittis, A G; Pedersen, P L; Mildvan, A S

    1995-05-10

    PP-50, a synthetic peptide, based on residues 141-190 of the beta-subunit of mitochondrial F1ATPase, containing the GX4GKT consensus sequence for nucleoside triphosphate binding, binds ATP tightly (Kd = 17.5 microM) as found by fluorescence titration at pH 4.0. CD and 2D proton NMR studies at pH 4.0 revealed two beta-turns, regions of extended secondary structure, transient tertiary structure, and flexibility in the GX4GKT region (W.J. Chuang, C. Abeygunawardana, P. L. Pedersen, and A. S. Mildvan, 1992, Biochemistry 31, 7915-7921). CD titration of PP-50 with trifluoroethanol (TFE) reveals a decrease in ellipticity at 208 and 222 nm, saturating at 25% TFE. Computer analysis indicates that 25% TFE increases the helix content from 5.8 to 28.6%, decreases the beta-structure from 30.2 to 20.2% and decreases the coil content from 64 to 51.2%. Fluorescence titrations of H2ATP2- with PP-50 in 25% TFE yields a Kd of 7.3 microM, 2.4-fold tighter than in H2O, probably due to TFE increasing the activity of H2ATP2- . PP-50 completely quenches the fluorescence of H2ATP2- in 25% TFE, while in H2O the fluorescence quenching is only 62%. In H2O the binding of H2ATP2- increases the structure of PP-50 as detected by CD, but in 25% TFE no significant change in CD is found on binding either H2ATP2- or Mg2+ HATP (Kd = 14 microM). The complete proton NMR spectrum of PP-50 in 25% TFE has been assigned. The solution structure, determined by distance geometry, molecular dynamics with simulated annealing, and energy minimization, consists of a coil (residues 1-8), a strand (residues 9-12), a loop (residues 13-22) containing the GX4GKT consensus sequence (residues 16-23), an alpha-helix (residues 23-36), a turn (residues 38-41), and a coil (residues 42-50), similar to that of the corresponding region of the X-ray structure of F1ATPase (J.P. Abrahams, A.G.W. Leslie, R. Lutter, and J. E. Walker, 1994 Nature 370, 621-628) and to the structure of a homologous peptide from the ATP-binding site of

  9. Further examination of seventeen mutations in Escherichia coli F1-ATPase beta-subunit.

    Science.gov (United States)

    Senior, A E; al-Shawi, M K

    1992-10-25

    Seventeen mutations in beta-subunit of Escherichia coli F1-ATPase which had previously been characterized in strain AN1272 (Mu-induced mutant) were expressed in strain JP17 (beta-subunit gene deletion). Six showed unchanged behavior, namely: C137Y; G142D; G146S; G207D; Y297F; and Y354F. Five failed to assemble F1F0 correctly, namely: G149I; G154I; G149I,G154I; G223D; and P403S,G415D. Six assembled F1F0 correctly, but with membrane ATPase lower than in AN1272, namely: K155Q; K155E; E181Q; E192Q; D242N; and D242V. AN1272 was shown to unexpectedly produce a small amount of wild-type beta-subunit; F1-ATPase activities reported previously in AN1272 were referable to hybrid enzymes containing both mutant and wild-type beta-subunits. Purified F1 was obtained from K155Q; K155E; E181Q; E192Q; and D242N mutants in JP17. Vmax ATPase values were lower, and unisite catalysis rate and equilibrium constants were perturbed to greater extent, than in AN1272. However, general patterns of perturbation revealed by difference energy diagrams were similar to those seen previously, and the new data correlated well in linear free energy relationships for reaction steps of unisite catalysis. Correlation between multisite and unisite ATPase activity was seen in the new enzymes. Overall, the data give strong support to previously proposed mechanisms of unisite catalysis, steady-state catalysis, and energy coupling in F1-ATPases (Al-Shawi, M. K., Parsonage, D. and Senior, A. E. (1990) J. Biol. Chem. 265, 4402-4410). The K155Q, K155E, D242N, and E181Q mutations caused 5000-fold, 4000-fold, 1800-fold, and 700-fold decrease, respectively, in Vmax ATPase, implying possibly direct roles for these residues in catalysis. Experiments with the D242N mutant suggested a role for residue beta D242 in catalytic site Mg2+ binding.

  10. Directed mutagenesis of the dicyclohexylcarbodiimide-reactive carboxyl residues in beta-subunit of F1-ATPase of Escherichia coli.

    Science.gov (United States)

    Parsonage, D; Wilke-Mounts, S; Senior, A E

    1988-02-15

    Previous studies in which dicyclohexylcarbodiimide (DCCD) was used to inactivate F1-ATPase enzymes have suggested that two glutamate residues in the beta-subunit are essential for catalysis. In the Escherichia coli F1-ATPase, these are residues beta-Glu-181 and beta-Glu-192. Oligonucleotide-directed mutagenesis was used to change these residues to beta-Gln-181 and beta-Gln-192. The beta-Gln-181 mutation produced strong impairment of oxidative phosphorylation in vivo and also of ATPase and ATP-driven proton-pumping activities in membranes assayed in vitro. A low level of each activity was detected and an F1-ATPase appeared to be assembled normally on the membranes. Therefore, it is suggested that the carboxyl side chain at residue beta-181 is important, although not absolutely required, for catalysis in both directions on E. coli F1-ATPase. The beta-Gln-192 mutation produced partial inhibition of oxidative phosphorylation in vivo and membrane ATPase activity was reduced by 78%. These results contrast with the complete or near-complete inactivation seen when E. coli F1-ATPase is reacted with DCCD and imply that DCCD-inactivation is attributable more to the attachment of the bulky DCCD molecule than to the derivatization of the carboxyl side chain of residue beta-Glu-192. M. Ohtsubo and colleagues (Biochem. Biophys. Res. Commun. (1987) 146, 705-710) described mutagenesis of the F1-beta-subunit of thermophilic bacterium PS3. Mutations (Glu----Gln) of the residues homologous to Glu-181 and Glu-192 of E. coli F1-beta-subunit both caused total inhibition of ATPase activity. Therefore, there was a marked difference in results obtained when the same residues were modified in the PS3 and E. coli F1-beta-subunits.

  11. Engineering a light-controlled F1 ATPase using structure-based protein design

    Directory of Open Access Journals (Sweden)

    Daniel Hoersch

    2016-07-01

    Full Text Available The F1 sub-complex of ATP synthase is a biological nanomotor that converts the free energy of ATP hydrolysis into mechanical work with an astonishing efficiency of up to 100% (Kinosita et al., 2000. To probe the principal mechanics of the machine, I re-engineered the active site of E.coli F1 ATPase with a structure-based protein design approach: by incorporation of a site-specific, photoswitchable crosslinker, whose end-to-end distance can be modulated by illumination with light of two different wavelengths, a dynamic constraint was imposed on the inter-atomic distances of the α and β subunits. Crosslinking reduced the ATP hydrolysis activity of four designs tested in vitro and in one case created a synthetic ATPase whose activity can be reversibly modulated by subsequent illumination with near UV and blue light. The work is a first step into the direction of the long-term goal to design nanoscaled machines based on biological parts that can be precisely controlled by light.

  12. Engineering a light-controlled F1 ATPase using structure-based protein design.

    Science.gov (United States)

    Hoersch, Daniel

    2016-01-01

    The F1 sub-complex of ATP synthase is a biological nanomotor that converts the free energy of ATP hydrolysis into mechanical work with an astonishing efficiency of up to 100% (Kinosita et al., 2000). To probe the principal mechanics of the machine, I re-engineered the active site of E.coli F1 ATPase with a structure-based protein design approach: by incorporation of a site-specific, photoswitchable crosslinker, whose end-to-end distance can be modulated by illumination with light of two different wavelengths, a dynamic constraint was imposed on the inter-atomic distances of the α and β subunits. Crosslinking reduced the ATP hydrolysis activity of four designs tested in vitro and in one case created a synthetic ATPase whose activity can be reversibly modulated by subsequent illumination with near UV and blue light. The work is a first step into the direction of the long-term goal to design nanoscaled machines based on biological parts that can be precisely controlled by light.

  13. Monoclonal antibodies to Escherichia coli F1-ATPase. Correlation of binding site location with interspecies cross-reactivity and effects on enzyme activity.

    Science.gov (United States)

    Dunn, S D; Tozer, R G; Antczak, D F; Heppel, L A

    1985-09-05

    Twenty-one hybridoma cell lines which secret antibodies to the subunits of the Escherichia coli F1-ATPase were produced. Included within the set are four antibodies which are specific for alpha, six for beta, three for gamma, four for delta and four for epsilon. The antibodies were divided into binding competition subgroups. Two such competition subgroups are represented for the alpha, beta, and epsilon subunits, one for delta and three for gamma. The ability to bind intact F1-ATPase was demonstrated for some of the antibodies to alpha and beta, and for all of those to delta, while the antibodies to gamma and epsilon gave unclear results. All of the antibodies to alpha and beta which bound ATPase were found to have effects on the ATPase activity of purified E. coli F1-ATPase. One of those to alpha inhibited activity by about 30%. Another anti-alpha was mildly stimulatory. The four antibodies to beta which bound ATPase inhibited activity by 90%. In contrast, membrane-bound ATPase was hardly affected by the antibodies to alpha, but was inhibited by 40-60% by the antibodies to beta. The other antibodies to alpha and beta bound only free subunits, or partially dissociated ATPase, suggesting that their epitopes are buried between subunits in ATPase. These antibodies had no effects on activity. The ability of the antibodies to recognize ATPase subunits present in crude extracts from mitochondria, chloroplasts, and a variety of bacteria was tested using nitrocellulose blots of sodium dodecyl sulfate-polyacrylamide gels. One anti-beta specifically recognized proteins in the range of 50,000-60,000 daltons in each of the extracts, although the reaction with mitochondrial beta was weak. Some of the other antibodies had limited cross-reaction, but most were specific for the E. coli protein. In some species, those proteins which were recognized by the anti-beta ran with a higher apparent molecular weight than proteins which were recognized by an anti-alpha. All antibodies which

  14. Abundance of Escherichia coli F1-ATPase molecules observed to rotate via single-molecule microscopy with gold nanorod probes.

    Science.gov (United States)

    York, Justin; Spetzler, David; Hornung, Tassilo; Ishmukhametov, Robert; Martin, James; Frasch, Wayne D

    2007-12-01

    The abundance of E. coli F1-ATPase molecules observed to rotate using gold nanorods attached to the gamma-subunit was quantitated. Individual F1 molecules were determined to be rotating based upon time dependent fluctuations of red and green light scattered from the nanorods when viewed through a polarizing filter. The average number of F1 molecules observed to rotate in the presence of GTP, ATP, and without nucleotide was approximately 50, approximately 25, and approximately 4% respectively. In some experiments, the fraction of molecules observed to rotate in the presence of GTP was as high as 65%. These data indicate that rotational measurements made using gold nanorods provide information of the F1-ATPase mechanism that is representative of the characteristics of the enzyme population as a whole.

  15. Ecto-F_1-ATPase: A moonlighting protein complex and an unexpected apoA-I receptor

    Institute of Scientific and Technical Information of China (English)

    Pierre; Vantourout; Claudia; Radojkovic; Laeticia; Lichtenstein; Véronique; Pons; Eric; Champagne; Laurent; O; Martinez

    2010-01-01

    Mitochondrial ATP synthase has been recently detected at the surface of different cell types, where it is a high affinity receptor for apoA-I, the major protein component in high density lipoproteins (HDL). Cell surface ATP synthase (namely ecto-F1-ATPase) expression is related to different biological effects, such as regulation of HDL uptake by hepatocytes, endothelial cell proliferation or antitumor activity of Vγ9/Vδ2 T lymphocytes. This paper reviews the recently discovered functions and regulations of ...

  16. Fluoroaluminum and fluoroberyllium nucleoside diphosphate complexes as probes of the enzymatic mechanism of the mitochondrial F1-ATPase.

    Science.gov (United States)

    Issartel, J P; Dupuis, A; Lunardi, J; Vignais, P V

    1991-05-14

    The mechanism by which fluoride and aluminum or beryllium in combination with ADP inhibit beef heart mitochondrial F1-ATPase was investigated. The kinetics of inhibition depended on the nature of the anion present in the F1-ATPase assay medium. Inhibition required the presence of Mg2+ and developed more rapidly with sulfite and sulfate than with chloride, i.e., with anions which activate F1-ATPase activity. The ADP-fluorometal complexes were bound quasi-irreversibly to F1, and each mole of the inhibitory nucleotide-fluorometal complex was tightly associated with 1 mol of Mg2+. One mole of nucleotide-fluorometal complex was able to inhibit the activity of 1 mol of catalytic site in F1. Direct measurements of bound fluoride, aluminum, beryllium, and ADP indicated that the F1-bound ADP-fluorometal complexes are of the following types: ADP1A11F4, ADP1Be1F1, ADP1Be1F2, or ADP1Be1F3. Fluoroaluminates or fluoroberyllates are isomorphous to Pi, and the inhibitory nucleotide-fluorometal complexes mimicked transient intermediates of nucleotides that appeared in the course of ATP hydrolysis. On the other hand, each mole of fully inhibited F1, retained 2 mol of inhibitory complexes. The same stoichiometry was observed when ADP was replaced by GDP, a nucleotide which, unlike ADP, binds only to the catalytic sites of F1. These results are discussed in terms of a stochastic model in which the three cooperative catalytic sites of F1 function in interactive pairs.

  17. Analysis of time-dependent change of Escherichia coli F1-ATPase activity and its relationship with apparent negative cooperativity.

    Science.gov (United States)

    Kato, Y; Sasayama, T; Muneyuki, E; Yoshida, M

    1995-10-10

    Except for the case of gradual activation of EF1 (F1-ATPase from Escherichia coli) caused by the dissociation of the epsilon subunit [Laget, P. P. and Smith, J. B. (1979) Arch. Biochem. Biophys. 197, 83-89], EF1 has long been thought not to show a time-dependent change in activity [Senior, A.E. et al. (1992) Arch. Biochem. Biophys. 297, 340-344]. Here, we report the time-dependent inactivation and activation of EF1, which are apparently similar to those of mitochondrial F1-ATPases [Vasilyeva, E.A. et al. (1982) Biochem. J. 202, 15-23]. Analysis of these changes as a function of ATP concentrations in relation to negative cooperativity revealed that the initial inactivation phase was attributable to the decrease in the Vmax associated with the low Km (around 10 microM), and the following activation, probably due to the dissociation of the epsilon subunit, corresponded to the increase in the Vmax associated with the high Km (in the order of 100 microM). Thus, the time-dependent change in EF1 activity is closely related to the apparent negative cooperativity (multiple Km values) of ATP hydrolysis.

  18. Lack of ability of trypsin-treated mitochondrial F1-ATPase to bind the oligomycin-sensitivity conferring protein (OSCP).

    Science.gov (United States)

    Hundal, T; Norling, B; Ernster, L

    1983-10-03

    Soluble beef-heart mitochondrial F1-ATPase modified in its alpha-subunit by mild trypsin treatment (alpha'-F1) can no longer bind oligomycin-sensitivity conferring protein (OSCP) but is still capable of binding to F1-depleted submitochondrial particles, giving rise to a maximally oligomycin-sensitive ATPase, provided the particles contain their native complement of OSCP. When OSCP is removed from the particles, alpha'-F1 can still bind to the particles, but added OSCP induces only a low degree of oligomycin sensitivity. The possible role of OSCP in the functional coupling of the catalytic (F1) and H+-translocating (Fo) moieties of mitochondrial ATPase is discussed. The results suggest a functional similarity between the OSCP component of mitochondrial ATPase and the delta-subunit of E. coli ATPase, which is in accordance with the structural homology recently found to exist between the two polypeptides.

  19. Complete kinetic and thermodynamic characterization of the unisite catalytic pathway of Escherichia coli F1-ATPase. Comparison with mitochondrial F1-ATPase and application to the study of mutant enzymes.

    Science.gov (United States)

    Al-Shawi, M K; Senior, A E

    1988-12-25

    A complete analysis is presented of the component rate constants of the "unisite" reaction pathway in normal Escherichia coli F1-ATPase. Gibbs free energy profiles of the unisite reaction pathway were constructed for both normal E. coli F1 and bovine-heart mitochondrial F1, and comparison indicated that E. coli F1 is an ancestral form of the mitochondrial enzyme. Similar kinetic and thermodynamic analyses of the unisite reaction pathway were done for mutant beta-Asn-242 and beta-Val-242 E. coli F1-ATPases. Both mutations affected unisite binding and hydrolysis of MgATP but had little effect on release of products or binding of MgADP. It was apparent that a primary effect of the mutations was on the interaction between the catalytic nucleotide-binding domain and the substrate MgATP. The catalytic transition state [F1-ATP]++ was the most destabilized step in the reaction sequence. Measurements of delta delta G[F1.ATP]++ and linear free energy plots for the catalytic step were consistent with the view that, in normal enzyme, residue beta-Asp-242 accepts an H-bond from the transition-state substrate in order to facilitate catalysis. Both mutations impaired positive catalytic cooperativity. This was caused by energetic destabilization of the catalytic transition state and was an indirect effect, not a direct effect on signal transmission per se between catalytic nucleotide-binding domains on beta-subunits. Therefore, impairment of unisite catalysis and of positive catalytic cooperativity appeared to be linked. This may provide a unifying explanation as to why a series of other, widely separated mis-sense mutations within the catalytic nucleotide-binding domain on F1-beta-subunit, which have been reported to affect unisite catalysis, also impair positive catalytic cooperativity. Linear free energy plots for the ATP-binding step of unisite catalysis demonstrated that beta-Asn-242 and beta-Val-242 mutant enzymes did not suffer any gross disruptive change in structure of

  20. Piceatannol, a stilbene phytochemical, inhibits mitochondrial F0F1-ATPase activity by targeting the F1 complex.

    Science.gov (United States)

    Zheng, J; Ramirez, V D

    1999-08-02

    Piceatannol is a stilbene phytochemical from the seeds of Euphorbia lagascae, previously identified as an antileukemic principle. Piceatannol is considered an inhibitor of several tyrosine kinases. We recently reported that resveratrol, another stilbene phytoalexin from grape seeds, was an inhibitor of ATP synthase. Here, we demonstrated that piceatannol potently inhibited the rat brain mitochondrial F0F1-ATPase activity in both solubilized and submitochondrial preparations (IC50 of 8-9 microM), while having relatively small effect on the Na(+), K(+)-ATPase activity of porcine cerebral cortex (no effect up to 7 microM). Piceatannol inhibited the ATPase activity of the purified rat liver F1 with IC50 of about 4 microM, while resveratrol was slightly less active (IC50 of about 14 microM). Our results indicate that piceatannol and resveratrol inhibit the F-type ATPase by targeting the F1 sector, which is located to the inner membrane of mitochondria and plasma membrane of normal endothelial cells and several cancer cell lines. This mechanism could potentially contribute to the multiple effects of these chemopreventive phytochemicals. Copyright 1999 Academic Press.

  1. Pi binding by the F1-ATPase of beef heart mitochondria and of the Escherichia coli plasma membrane.

    Science.gov (United States)

    Penefsky, Harvey S

    2005-04-11

    Pi binding by the F(1)-ATPase of beef heart mitochondria and of the Escherichia coli plasma membrane (E. coli F(1)) was examined by two methods: the centrifuge column procedure [Penefsky, H.S. (1977) J. Biol. Chem. 252, 2891-2899] and the Paulus pressure dialysis cell [Paulus, H. (1969) Anal. Biochem. 32, 91-100]. The latter is an equilibrium dialysis-type procedure. Pi binding by beef heart F(1) could be determined by either procedure. However, direct binding of Pi to E. coli F(1) could be determined adequately only in the Paulus cell which indicated more than two binding sites per mol of enzyme with a K(d) in the range of 0.1 mM. It is concluded that previous failure to observe Pi binding to E. coli F(1) with the centrifuge column procedure is due to a rapid rate of dissociation of Pi from the E. coli enzyme which results in loss of Pi during transit of the enzyme-Pi complex through the column.

  2. Effective rates from thermodynamically consistent coarse-graining of models for molecular motors with probe particles.

    Science.gov (United States)

    Zimmermann, Eva; Seifert, Udo

    2015-02-01

    Many single-molecule experiments for molecular motors comprise not only the motor but also large probe particles coupled to it. The theoretical analysis of these assays, however, often takes into account only the degrees of freedom representing the motor. We present a coarse-graining method that maps a model comprising two coupled degrees of freedom which represent motor and probe particle to such an effective one-particle model by eliminating the dynamics of the probe particle in a thermodynamically and dynamically consistent way. The coarse-grained rates obey a local detailed balance condition and reproduce the net currents. Moreover, the average entropy production as well as the thermodynamic efficiency is invariant under this coarse-graining procedure. Our analysis reveals that only by assuming unrealistically fast probe particles, the coarse-grained transition rates coincide with the transition rates of the traditionally used one-particle motor models. Additionally, we find that for multicyclic motors the stall force can depend on the probe size. We apply this coarse-graining method to specific case studies of the F(1)-ATPase and the kinesin motor.

  3. Determination of the 1-ethyl-3-[(3-dimethylamino)propyl]-carbodiimide- induced cross-link between the beta and epsilon subunits of Escherichia coli F1-ATPase.

    Science.gov (United States)

    Dallmann, H G; Flynn, T G; Dunn, S D

    1992-09-15

    The zero-length cross-link between the inhibitory epsilon subunit and one of three catalytic beta subunits of Escherichia coli F1-ATPase (alpha 3 beta 3 gamma delta epsilon), induced by a water-soluble carbodiimide, 1-ethyl-3-[(3-dimethylamino) propyl]-carbodiimide (EDC), has been determined at the amino acid level. Lability of cross-linked beta-epsilon to base suggested an ester cross-link rather than the expected amide. A 10-kDa cross-linked CNBr fragment derived from beta-epsilon was identified by electrophoresis on high percentage polyacrylamide gels. Sequence analysis of this peptide revealed the constituent peptides to be Asp-380 to Met-431 of beta and Glu-96 to Met-138 of epsilon. Glu-381 of beta was absent from cycle 2 indicating that it was one of the cross-linked residues, but no potential cross-linked residue in epsilon was identified in this analysis. A form of epsilon containing a methionine residue in place of Val-112 (epsilon V112M) was produced by site-directed mutagenesis. epsilon V112M was incorporated into F1-ATPase which was then cross-linked with EDC. An 8-kDa cross-linked CNBr fragment of beta-epsilon V112M was shown to contain the peptide of epsilon between residues Glu-96 and Met-112 and the peptide of beta between residues Asp-380 and Met-431. Again residue Glu-381 of beta was notably reduced and no missing residue from the epsilon peptide could be identified, but the peptide sequence limited the possible choices to Ser-106, Ser-107, or Ser-108. Furthermore, an epsilon mutant in which Ser-108 was replaced by cysteine could no longer be cross-linked to a beta subunit in F1-ATPase by EDC. Both mutant forms of epsilon supported growth of an uncC-deficient E. coli strain and inhibited F1-ATPase. These results indicate that the EDC-induced cross-link between the beta and epsilon subunits of F1-ATPase is an ester linkage between beta-Glu-381 and, likely, epsilon-Ser-108. As these residues must be located immediately adjacent to one another in F1

  4. Engineering Nanoscale Biological Molecular Motors

    OpenAIRE

    Korosec, Chapin; Forde, Nancy R.

    2017-01-01

    Understanding the operation of biological molecular motors, nanoscale machines that transduce electrochemical energy into mechanical work, is enhanced by bottom-up strategies to synthesize novel motors.

  5. ATP-binding site of adenylate kinase: mechanistic implications of its homology with ras-encoded p21, F1-ATPase, and other nucleotide-binding proteins.

    Science.gov (United States)

    Fry, D C; Kuby, S A; Mildvan, A S

    1986-02-01

    The MgATP binding site of adenylate kinase, located by a combination of NMR and x-ray diffraction, is near three protein segments, five to seven amino acids in length, that are homologous in sequence to segments found in other nucleotide-binding phosphotransferases, such as myosin and F1-ATPase, ras p21 and transducin GTPases, and cAMP-dependent and src protein kinases, suggesting equivalent mechanistic roles of these segments in all of these proteins. Segment 1 is a glycine-rich flexible loop that, on adenylate kinase, may control access to the ATP-binding site by changing its conformation. Segment 2 is an alpha-helix containing two hydrophobic residues that interact with the adenine-ribose moiety of ATP, and a lysine that may bind to the beta- and gamma-phosphates of ATP. Segment 3 is a hydrophobic strand of parallel beta-pleated sheet, terminated by a carboxylate, that flanks the triphosphate binding site. The various reported mutations of ras p21 that convert it to a transforming agent all appear to involve segment 1, and such substitutions may alter the properties of p21 by hindering a conformational change at this segment. In F1-ATPase, the flexible loop may, by its position, control both the accessibility and the ATP/ADP equilibrium constant on the enzyme.

  6. Reconstitution of F1-ATPase activity from Escherichia coli subunits alpha, beta and subunit gamma tagged with six histidine residues at the C-terminus.

    Science.gov (United States)

    Ekuni, A; Watanabe, H; Kuroda, N; Sawada, K; Murakami, H; Kanazawa, H

    1998-05-01

    An engineered gamma subunit of Escherichia coli F1-ATPase with extra 14 and 20 amino acid residues at the N- and C-termini (His-tag gamma), respectively, was overproduced in E. coli and purified. Six histidines are included in the C-terminal extension. The reconstituted F1 containing alpha, beta, and His-tagged gamma exhibited sixty percent of the wild-type ATPase activity. The reconstituted alphabeta His-tag gamma complex was subjected to affinity chromatography with nickel-nitrilotriacetic acid (Ni-NTA) agarose resin. ATPase activity was eluted specifically with imidazole. These results implied that the tag sequence protruded to the surface of the complex and did not seriously impair the activity. The reconstituted alphabeta His-tag gamma complex, even after its binding to the resin, exhibited ATPase activity suggesting that the gamma subunit, when fixed to a solid phase, may rotate the alphabeta complex. This system may provide a new approach for analysis of the rotation mechanisms in F1-ATPase.

  7. Light-driven molecular motors

    OpenAIRE

    van Delden, RA; FERINGA, BL; Kuzmany, H.; Fink, J.; Mehring, M.; Roth, S.

    2004-01-01

    Molecular motors can be defined as molecules that are able to convert any type of energy input (a fuel) into controlled motion. These systems can be categorized into linear and rotary motors, depending on the motion induced. This brief account will discuss the state of affairs of the research on light-driven rotary molecular motors.

  8. ATP-dependent inactivation of the beta-Ser339Cys mutant F1-ATPase from Escherichia coli by N-ethylmaleimide.

    Science.gov (United States)

    Schmidt, G; Senior, A E

    1995-08-01

    We introduced mutations at the highly-conserved residue Ser-339 in subunit beta of Escherichia coli F1-ATPase. The mutations beta S339Y and beta S339F abolished ATPase activity and impaired enzyme assembly. In contrast beta S339C F1 retained function to a substantial degree. N-Ethylmaleimide (NEM) at 0.2-0.3 mM inactivated beta S339C F1-ATPase by 80-95% in the presence of MgATP or MgADP but did not inactivate appreciably in absence of nucleotide or presence of EDTA. In absence of nucleotide, 0.7 mol of [14C-NEM] was incorporated into beta-subunits of 1.0 mol F1: in presence of MgATP the amount was 1.7 mol/mol, i.e. the introduced Cys residue became more accessible to reaction in the presence of MgATP. In the X-ray structure of F1 (Abrahams et al. (1994) Nature 370, 621-628) one of the catalytic nucleotide-binding domains is empty (on the "beta E subunit") and contains a cleft. Residue beta-339 lies within this cleft; the cleft does not occur in the other two beta-subunits. Our data are consistent with the conclusion that in wild-type enzyme under physiological conditions, MgATP or MgADP induce an enzyme conformation in which residue beta-Ser-339 becomes more exposed, possibly similar to the situation seen in the "beta E-subunit" in the X-ray structure.

  9. The subunit b dimer of the FOF1-ATP synthase: interaction with F1-ATPase as deduced by site-specific spin-labeling.

    Science.gov (United States)

    Motz, Christian; Hornung, Tassilo; Kersten, Michael; McLachlin, Derek T; Dunn, Stanley D; Wise, John G; Vogel, Pia D

    2004-11-19

    We have used site-specific spin-labeling of single cysteine mutations within a water-soluble mutant of subunit b of the ATP synthase and employed electron spin resonance (ESR) spectroscopy to obtain information about the binding interactions of the b dimer with F1-ATPase. Interaction of b2 with a delta-depleted F1 (F1-delta) was also studied. The cysteine mutations used for spin-labeling were distributed throughout the cytosolic domain of the b subunit. In addition, each position between residues 101 and 114 of b was individually mutated to cysteine. All mutants were modified with a cysteine-reactive spin label. The room temperature ESR spectra of spin-labeled b2 in the presence of F1 or F1-delta when compared with the spectra of free b2 indicate a tight binding interaction between b2 and F1. The data suggest that b2 packs tightly to F1 between residues 80 and the C terminus but that there are segments of b2 within that region where packing interactions are quite loose. Two-dimensional gel electrophoresis confirmed binding of the modified b mutants to F1-ATPase as well as to F1-delta. Subsequent addition of delta to F1-delta.b2 complex resulted in changes in the ESR spectra, indicating different binding interactions of b to F1 in the presence or absence of delta. The data also suggest that the reconstitution of the ATP synthase is not ordered with respect to these subunits. Additional spectral components observed in b preparations that were spin-labeled between amino acid position 101 and 114 are indicative of either two populations of b subunits with different packing interactions or to helical bending within this region.

  10. Cloning and Characterization of an mRNA Encoding F1-ATPase Beta-Subunit Abundant in Epithelial Cells of Mantle and Gill of Pearl Oyster, Pinctadafucata

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In oyster biomineralization, large amounts of calcium are absorbed from external media, transported to the mineralization site, and finally deposited via a matrix-mediated process. All these activities are very energy intensive; therefore, investigations of the energy metabolism pathways of different oyster tissues will facilitate understanding of oyster biomineralization physiology. A full-length cDNA encoding the F1-ATPase beta-subunit (the F1-β-subunit, a major calalytic subunit of F-ATPase) from the pearl oyster (Pinctads fucata) was cloned using the homology strategy with a pair of degenerated primers based on the conserved regions of other animals' F1-β-subunit genes. Sequencing and structural analyses showed that the obtained sequence shared high identity with other animals' F1-β-subunits, and had a unique phosphorylation site of PKC and CK Ⅱ on the external surface of the putative protein. Results from semi-quantitative reverse transcription-polymerase chain reaction and in situ hybridization demonstrated this oyster F1-β-subunit mRNA is abundant in the gill and mantle, and distributed widely in the periostracal groove, the outer folder,and the dorsal region of the mantle and in the gill epithelial cells. These tissues were the main regions that participate in biomineralization processes such as calcium uptake, transport, and matrix secretion. The results indicate that tissues involved in biomineralization have stronger energy metabolic processes and that F1-ATPase might play an important role in oyster biomineralization by providing energy transport.

  11. An intact F1ATPase alpha-subunit gene and a pseudogene with differing genomic organization are detected in both male-fertile and CMS petunia mitochondria.

    Science.gov (United States)

    Yesodi, V; Hauschner, H; Tabib, Y; Firon, N

    1997-11-01

    The gene copies for the alpha-subunit of the mitochondrial F1ATPase (atpA) were isolated and characterized in both male-fertile and cytoplasmic male sterile (CMS) petunia. Two copies, an intact gene and a truncated gene, were detected in both cytoplasms. The accumulated data, based upon a comparison of the sequences (the open reading frames as well as the 5' and 3' flanking regions) of the two atpA copies, both in male-fertile and CMS Petunia, indicate that: (1) they differ in their genomic organization and (2) a common progenitor cytoplasm, containing two copies of an intact atpA sequence, served as the origin for the atpA copies of the fertility and CMS-inducing cytoplasms. Homologous recombination through the progenitor intact atpA sequences is assumed to have caused the rearrangement in the 3' portion of the atpA open reading frame and the generation of the truncated atpA gene. It is thus suggested that the atpA pseudogenes, in both male-fertile and CMS cytoplasms, originated from a common progenitor atpA pseudogene sequence.

  12. Expression of the wild-type and the Cys-/Trp-less alpha 3 beta 3 gamma complex of thermophilic F1-ATPase in Escherichia coli.

    Science.gov (United States)

    Matsui, T; Yoshida, M

    1995-09-12

    The alpha, beta and gamma subunits of F1-ATPase from thermophilic Bacillus PS3 were expressed in Escherichia coli cells simultaneously in large amounts. Most of the expressed subunits assembled into a form of alpha 3 beta 3 gamma complex in E. coli cells and this complex was easily purified to homogeneity. The recombinant alpha 3 beta 3 gamma complex thus obtained showed similar enzymatic properties to the alpha 3 beta 3 gamma complex obtained by in vitro reconstitution from individual subunits (Yokoyama, K. et al. (1989) J. Biol. Chem. 264, 21837-21841) except that the former had several-fold higher ATPase activity than the latter. Using this expression system, a mutant alpha 3 beta 3 gamma complex with no Trp and Cys was generated by replacing alpha Cys193 and alpha Trp463 with Ser and Phe, respectively. This mutant complex was functionally intact, indicating both residues are not essential for catalysis. The Cys-/Trp-less complex is a convenient 'second wild type' enzyme from which one can generate mutants with Trp (as a fluorescent probe) or Cys (as an acceptor of a variety of probes) at desired positions without concern for 'background' Trp and Cys residues.

  13. Phylogenetic analyses of the homologous transmembrane channel-forming proteins of the F0F1-ATPases of bacteria, chloroplasts and mitochondria.

    Science.gov (United States)

    Blair, A; Ngo, L; Park, J; Paulsen, I T; Saier, M H

    1996-01-01

    Sequences of the three integral membrane subunits (subunits a, b and c) of the F0 sector of the proton-translocating F-type (F0F1-) ATPases of bacteria, chloroplasts and mitochondria have been analysed. All homologous-sequenced proteins of these subunits, comprising three distinct families, have been identified by database searches, and the homologous protein sequences have been aligned and analysed for phylogenetic relatedness. The results serve to define the relationships of the members of each of these three families of proteins, to identify regions of relative conservation, and to define relative rates of evolutionary divergence. Of these three subunits, c-subunits exhibited the slowest rate of evolutionary divergence, b-subunits exhibited the most rapid rate of evolutionary divergence, and a-subunits exhibited an intermediate rate of evolutionary divergence. The results allow definition of the relative times of occurrence of specific events during evolutionary history, such as the intragenic duplication event that gave rise to large c-subunits in eukaryotic vacuolar-type ATPases after eukaryotes diverged from archaea, and the extragenic duplication of F-type ATPase b-subunits that occurred in blue-green bacteria before the advent of chloroplasts. The results generally show that the three F0 subunits evolved as a unit from a primordial set of genes without appreciable horizontal transmission of the encoding genetic information although a few possible exceptions were noted.

  14. Structure of a thermophilic F1-ATPase inhibited by an ε-subunit: deeper insight into the ε-inhibition mechanism.

    Science.gov (United States)

    Shirakihara, Yasuo; Shiratori, Aya; Tanikawa, Hiromi; Nakasako, Masayoshi; Yoshida, Masasuke; Suzuki, Toshiharu

    2015-08-01

    F1-ATPase (F1) is the catalytic sector in F(o)F1-ATP synthase that is responsible for ATP production in living cells. In catalysis, its three catalytic β-subunits undergo nucleotide occupancy-dependent and concerted open-close conformational changes that are accompanied by rotation of the γ-subunit. Bacterial and chloroplast F1 are inhibited by their own ε-subunit. In the ε-inhibited Escherichia coli F1 structure, the ε-subunit stabilizes the overall conformation (half-closed, closed, open) of the β-subunits by inserting its C-terminal helix into the α3β3 cavity. The structure of ε-inhibited thermophilic F1 is similar to that of E. coli F1, showing a similar conformation of the ε-subunit, but the thermophilic ε-subunit stabilizes another unique overall conformation (open, closed, open) of the β-subunits. The ε-C-terminal helix 2 and hook are conserved between the two structures in interactions with target residues and in their positions. Rest of the ε-C-terminal domains are in quite different conformations and positions, and have different modes of interaction with targets. This region is thought to serve ε-inhibition differently. For inhibition, the ε-subunit contacts the second catches of some of the β- and α-subunits, the N- and C-terminal helices, and some of the Rossmann fold segments. Those contacts, as a whole, lead to positioning of those β- and α- second catches in ε-inhibition-specific positions, and prevent rotation of the γ-subunit. Some of the structural features are observed even in IF1 inhibition in mitochondrial F1.

  15. Gene fusions with human carbonic anhydrase II for efficient expression and rapid single-step recovery of recombinant proteins: expression of the Escherichia coli F1-ATPase epsilon subunit.

    Science.gov (United States)

    Van Heeke, G; Shaw, R; Schnizer, R; Couton, J M; Schuster, S M; Wagner, F W

    1993-08-01

    A new expression vector was constructed which allows the overproduction in Escherichia coli of tripartite proteins consisting of human carbonic anhydrase isozyme II (hCAII), a peptide linker containing an enterokinase cleavage site, and a target protein of interest. Carbonic anhydrase is soluble and stable in E. coli and serves as a highly specific purification tag in the recovery of the fusion protein by a single affinity chromatography step. The enterokinase cleavage site was engineered into the construct to allow accurate and efficient release of the target protein. To demonstrate the practical value of this vector, the E. coli F1-ATPase epsilon subunit was expressed as a fusion with hCAII. After a single purification step, biologically active recombinant E. coli F1-ATPase epsilon subunit was recovered following proteolytic removal of the hCAII moiety.

  16. Detecting proton flux across chromatophores driven by F0F1-ATPase using N-(fluorescein-5-thiocarbamoyl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt.

    Science.gov (United States)

    Yuanbo, Cui; Fan, Zhang; Jiachang, Yue

    2005-09-01

    N-(Fluorescein-5-thiocarbamoyl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt (F-DHPE) is a lipid fluorescence dye sensitive to pH changes and is used in this study for detecting proton flux through F0F1-ATPase within chromatophores driven by ATP hydrolysis. F-DHPE is easily labeled to the outer surface of chromatophores. In the range of pH 7.0 to 9.0, fluorescence intensity is sensitive to pH changes. The sensitivity is especially great in the range of pH 8.2 to 9.0, so pH 8.6 was chosen as the appropriate experimental condition. It is shown that added ATP not only acts as a fluorescence quencher but also can be hydrolyzed by F0F1-ATPase to pump protons into chromatophores, resulting in fluorescence restoration. A stimulator (NaSO3) and various types of inhibitors (NaN3, 5'-adenylyl imidodiphosphate [AMP-PNP], and N,N'-dicyclohexylcarbodiimide [DCCD]) of F0F1 confirmed that fluorescence restoration is caused by ATP-driven proton flux. When loaded with one antibody (anti-beta antibody) or two antibodies (anti-beta antibody and sheep to rabbit second antibody), F0F1-ATPase exhibits lower proton pumping activities, as indicated by fluorescence restoration. The possible mechanism of the inhibition of antibodies on proton pumping activity is discussed.

  17. Fluctuation Relations for Molecular Motors

    Science.gov (United States)

    Lacoste, David; Mallick, Kirone

    This review is focused on the application of specific fluctuation relations, such as the Gallavotti-Cohen relation, to ratchet models of a molecular motor. A special emphasis is placed on two-state models such as the flashing ratchet model. We derive the Gallavotti-Cohen fluctuation relation for these models and we discuss some of its implications.

  18. Nanotechnology Review: Molecular Electronics to Molecular Motors

    Science.gov (United States)

    Srivastava, Deepak; Saini, Subhash (Technical Monitor)

    1998-01-01

    Reviewing the status of current approaches and future projections, as already published in scientific journals and books, the talk will summarize the direction in which computational and experimental nanotechnologies are progressing. Examples of nanotechnological approaches to the concepts of design and simulation of carbon nanotube based molecular electronic and mechanical devices will be presented. The concepts of nanotube based gears and motors will be discussed. The above is a non-technical review talk which covers long term precompetitive basic research in already published material that has been presented before many US scientific meeting audiences.

  19. Localization of P42 and F(1)-ATPase α-subunit homolog of the gliding machinery in Mycoplasma mobile revealed by newly developed gene manipulation and fluorescent protein tagging.

    Science.gov (United States)

    Tulum, Isil; Yabe, Masaru; Uenoyama, Atsuko; Miyata, Makoto

    2014-05-01

    Mycoplasma mobile has a unique mechanism that enables it to glide on solid surfaces faster than any other gliding mycoplasma. To elucidate the gliding mechanism, we developed a transformation system for M. mobile based on a transposon derived from Tn4001. Modification of the electroporation conditions, outgrowth time, and colony formation from the standard method for Mycoplasma species enabled successful transformation. A fluorescent-protein tagging technique was developed using the enhanced yellow fluorescent protein (EYFP) and applied to two proteins that have been suggested to be involved in the gliding mechanism: P42 (MMOB1050), which is transcribed as continuous mRNA with other proteins essential for gliding, and a homolog of the F1-ATPase α-subunit (MMOB1660). Analysis of the amino acid sequence of P42 by PSI-BLAST suggested that P42 evolved from a common ancestor with FtsZ, the bacterial tubulin homologue. The roles of P42 and the F(1)-ATPase subunit homolog are discussed as part of our proposed gliding mechanism.

  20. Localization of P42 and F1-ATPase α-Subunit Homolog of the Gliding Machinery in Mycoplasma mobile Revealed by Newly Developed Gene Manipulation and Fluorescent Protein Tagging

    Science.gov (United States)

    Tulum, Isil; Yabe, Masaru; Uenoyama, Atsuko

    2014-01-01

    Mycoplasma mobile has a unique mechanism that enables it to glide on solid surfaces faster than any other gliding mycoplasma. To elucidate the gliding mechanism, we developed a transformation system for M. mobile based on a transposon derived from Tn4001. Modification of the electroporation conditions, outgrowth time, and colony formation from the standard method for Mycoplasma species enabled successful transformation. A fluorescent-protein tagging technique was developed using the enhanced yellow fluorescent protein (EYFP) and applied to two proteins that have been suggested to be involved in the gliding mechanism: P42 (MMOB1050), which is transcribed as continuous mRNA with other proteins essential for gliding, and a homolog of the F1-ATPase α-subunit (MMOB1660). Analysis of the amino acid sequence of P42 by PSI-BLAST suggested that P42 evolved from a common ancestor with FtsZ, the bacterial tubulin homologue. The roles of P42 and the F1-ATPase subunit homolog are discussed as part of our proposed gliding mechanism. PMID:24509320

  1. Duty ratio of cooperative molecular motors.

    Science.gov (United States)

    Dharan, Nadiv; Farago, Oded

    2012-02-01

    Molecular motors are found throughout the cells of the human body and have many different and important roles. These micromachines move along filament tracks and have the ability to convert chemical energy into mechanical work that powers cellular motility. Different types of motors are characterized by different duty ratios, which is the fraction of time that a motor is attached to its filament. In the case of myosin II (a nonprocessive molecular machine with a low duty ratio), cooperativity between several motors is essential to induce motion along its actin filament track. In this work we use statistical mechanical tools to calculate the duty ratio of cooperative molecular motors. The model suggests that the effective duty ratio of nonprocessive motors that work in cooperation is lower than the duty ratio of the individual motors. The origin of this effect is the elastic tension that develops in the filament which is relieved when motors detach from the track.

  2. Molecular motors and their functions in plants

    Science.gov (United States)

    Reddy, A. S.

    2001-01-01

    Molecular motors that hydrolyze ATP and use the derived energy to generate force are involved in a variety of diverse cellular functions. Genetic, biochemical, and cellular localization data have implicated motors in a variety of functions such as vesicle and organelle transport, cytoskeleton dynamics, morphogenesis, polarized growth, cell movements, spindle formation, chromosome movement, nuclear fusion, and signal transduction. In non-plant systems three families of molecular motors (kinesins, dyneins, and myosins) have been well characterized. These motors use microtubules (in the case of kinesines and dyneins) or actin filaments (in the case of myosins) as tracks to transport cargo materials intracellularly. During the last decade tremendous progress has been made in understanding the structure and function of various motors in animals. These studies are yielding interesting insights into the functions of molecular motors and the origin of different families of motors. Furthermore, the paradigm that motors bind cargo and move along cytoskeletal tracks does not explain the functions of some of the motors. Relatively little is known about the molecular motors and their roles in plants. In recent years, by using biochemical, cell biological, molecular, and genetic approaches a few molecular motors have been isolated and characterized from plants. These studies indicate that some of the motors in plants have novel features and regulatory mechanisms. The role of molecular motors in plant cell division, cell expansion, cytoplasmic streaming, cell-to-cell communication, membrane trafficking, and morphogenesis is beginning to be understood. Analyses of the Arabidopsis genome sequence database (51% of genome) with conserved motor domains of kinesin and myosin families indicates the presence of a large number (about 40) of molecular motors and the functions of many of these motors remain to be discovered. It is likely that many more motors with novel regulatory

  3. Relationship of proton motive force and the F(0)F (1)-ATPase with bio-hydrogen production activity of Rhodobacter sphaeroides: effects of diphenylene iodonium, hydrogenase inhibitor, and its solvent dimethylsulphoxide.

    Science.gov (United States)

    Hakobyan, Lilit; Gabrielyan, Lilit; Trchounian, Armen

    2012-08-01

    Rhodobacter sphaeroides MDC 6521 was able to produce bio-hydrogen (H(2)) in anaerobic conditions under illumination. In this study the effects of the hydrogenase inhibitor-diphenylene iodonium (Ph(2)I) and its solvent dimethylsulphoxide (DMSO) on growth characteristics and H(2) production by R. sphaeroides were investigated. The results point out the concentration dependent DMSO effect: in the presence of 10 mM DMSO H(2) yield was ~6 fold lower than that of the control. The bacterium was unable to produce H(2) in the presence of Ph(2)I. In order to examine the mediatory role of proton motive force (∆p) or the F(0)F(1)-ATPase in H(2) production by R. sphaeroides, the effects of Ph(2)I and DMSO on ∆p and its components (membrane potential (∆ψ) and transmembrane pH gradient), and ATPase activity were determined. In these conditions ∆ψ was of -98 mV and the reversed ∆pH was +30 mV, resulting in ∆p of -68 mV. Ph(2)I decreased ∆ψ in concentrations of 20 μM and higher; lower concentrations of Ph(2)I as DMSO had no valuable effect on ∆ψ. The R. sphaeroides membrane vesicles demonstrated significant ATPase activity sensitive to N,N'-dicyclohexylcarbodiimide. The 10-20 μM Ph(2)I did not affect the ATPase activity, whereas 40 μM Ph(2)I caused a marked inhibition (~2 fold) in ATPase activity. The obtained results provide novel evidence on the involvement of hydrogenase and the F(0)F(1)-ATPase in H(2) production by R. sphaeroides. Moreover, these data indicate the role of hydrogenase and the F(0)F(1)-ATPase in ∆p generation. In addition, DMSO might increase an interaction of nitrogenase with CO(2), decreasing nitrogenase activity and affecting H(2) production.

  4. In vivo affinity label of a protein expressed in Escherichia coli. Coenzyme A occupied the AT(D)P binding site of the mutant F1-ATPase beta subunit (Y307C) through a disulfide bond.

    Science.gov (United States)

    Odaka, M; Kiribuchi, K; Allison, W S; Yoshida, M

    1993-12-27

    When Tyr-307 of the beta subunit of F1-ATPase from a thermophilic Bacillus strain PS3 is replaced by cysteine and expressed in Escherichia coli cells, about a half population of the mutant beta subunit are labeled by Coenzyme A at Cys-307 through a disulfide bond which is cleavable by reducing treatment. The mutant beta subunit can be reconstituted into the alpha 3 beta 3 complex of which ATPase activity is stimulated two-fold by reducing treatment either prior or after reconstitution. Since Tyr-307 has been supposed to be located at one of subdomains which form the ATP binding site of the beta subunit, Coenzyme A binds to the mutant beta subunit as an AT(D)P analogue in E. coli cells and then covalently attaches to Cys-307.

  5. Molecular Motors: Power Strokes Outperform Brownian Ratchets.

    Science.gov (United States)

    Wagoner, Jason A; Dill, Ken A

    2016-07-07

    Molecular motors convert chemical energy (typically from ATP hydrolysis) to directed motion and mechanical work. Their actions are often described in terms of "Power Stroke" (PS) and "Brownian Ratchet" (BR) mechanisms. Here, we use a transition-state model and stochastic thermodynamics to describe a range of mechanisms ranging from PS to BR. We incorporate this model into Hill's diagrammatic method to develop a comprehensive model of motor processivity that is simple but sufficiently general to capture the full range of behavior observed for molecular motors. We demonstrate that, under all conditions, PS motors are faster, more powerful, and more efficient at constant velocity than BR motors. We show that these differences are very large for simple motors but become inconsequential for complex motors with additional kinetic barrier steps.

  6. Molecular switches and motors on surfaces.

    Science.gov (United States)

    Pathem, Bala Krishna; Claridge, Shelley A; Zheng, Yue Bing; Weiss, Paul S

    2013-01-01

    Molecular switches and motors respond structurally, electronically, optically, and/or mechanically to external stimuli, testing and potentially enabling extreme miniaturization of optoelectronic devices, nanoelectromechanical systems, and medical devices. The assembly of motors and switches on surfaces makes it possible both to measure the properties of individual molecules as they relate to their environment and to couple function between assembled molecules. In this review, we discuss recent progress in assembling molecular switches and motors on surfaces, measuring static and dynamic structures, understanding switching mechanisms, and constructing functional molecular materials and devices. As demonstrative examples, we choose a representative molecule from three commonly studied classes including molecular switches, photochromic molecules, and mechanically interlocked molecules. We conclude by offering perspectives on the future of molecular switches and motors on surfaces.

  7. Loose mechanochemical coupling of molecular motors

    CERN Document Server

    Zhang, Yunxin

    2011-01-01

    In living cells, molecular motors convert chemical energy into mechanical work. Its thermodynamic energy efficiency, i.e. the ratio of output mechanical work to input chemical energy, is usually high. However, using two-state models, we found the motion of molecular motors is loosely coupled to the chemical cycle. Only part of the input energy can be converted into mechanical work. Others is dissipated into environment during substeps without contributions to the macro scale unidirectional movement.

  8. Duty-ratio of cooperative molecular motors

    CERN Document Server

    Dharan, Nadiv

    2012-01-01

    Molecular motors are found throughout the cells of the human body, and have many different and important roles. These micro-machines move along filament tracks, and have the ability to convert chemical energy into mechanical work that powers cellular motility. Different types of motors are characterized by different duty-ratios, which is the fraction of time that a motor is attached to its filament. In the case of myosin II - a non-processive molecular machine with a low duty ratio - cooperativity between several motors is essential to induce motion along its actin filament track. In this work we use statistical mechanical tools to calculate the duty ratio of cooperative molecular motors. The model suggests that the effective duty ratio of non-processive motors that work in cooperation is lower than the duty ratio of the individual motors. The origin of this effect is the elastic tension that develops in the filament which is relieved when motors detach from the track.

  9. Structural features of the γ subunit of the Escherichia coli F1 ATPase revealed by a 4.4-Å resolution map obtained by x-ray crystallography

    OpenAIRE

    1999-01-01

    The F1 part of the F1FO ATP synthase from Escherichia coli has been crystallized and its structure determined to 4.4-Å resolution by using molecular replacement based on the structure of the beef-heart mitochondrial enzyme. The bacterial F1 consists of five subunits with stoichiometry α3, β3, γ, δ, and ɛ. δ was removed before crystallization. In agreement with the structure of the beef-heart mitochondrial enzyme, although not that from rat liver, the present study suggests that the α and β su...

  10. Bio-inspired novel design principles for artificial molecular motors.

    Science.gov (United States)

    Hugel, Thorsten; Lumme, Christina

    2010-10-01

    Since we have learned that biological organisms like ourselves are driven by tiny biological molecular motors we try to design and produce artificial molecular motors. However, despite the huge efforts since decades, man-made artificial molecular motors are still far from biological molecular motors or macroscopic motors with regard to performance, especially with respect to energy efficiency. This review highlights recent progress towards artificial molecular motors and discusses how their design and development can be guided by the design concepts of biological molecular motors or macroscopic motors.

  11. Complete inhibition of the tentoxin-resistant F1-ATPase from Escherichia coli by the phytopathogenic inhibitor tentoxin after substitution of critical residues in the alpha - and beta -subunit.

    Science.gov (United States)

    Schnick, Claudia; Körtgen, Nicole; Groth, Georg

    2002-12-27

    Substitution of critical residues in the alpha- and beta-subunit can turn the typically resistant ATP synthase from the bacterium Escherichia coli into an enzyme showing high sensitivity to the phytopathogenic inhibitor tentoxin, which usually affects only certain sensitive plant species. In contrast to recent results obtained with the thermophilic F(1) (Groth, G., Hisabori, T., Lill, H., and Bald, D. (2002) J. Biol. Chem. 277, 20117-20119), substitution of a critical serine in the beta-subunit (betaSer(59)), which is supposed to provide an important intermolecular hydrogen bond in the binding site, was not sufficient on its own for conferring tentoxin sensitivity to the E. coli F(1) complex. Superimposition of the chloroplast F(1)-tentoxin inhibitor complex on a homology model of the E. coli F(1) complex provided detailed information on the critical residues in the alpha-subunit of the binding cleft and allowed us to model the binding site according to the steric requirements of the inhibitor. Substitution of the highly conserved residue alphaLeu(64) seems to be most important for allowing access of the inhibitor to the binding site. Combining this substitution with either additional replacements in the alpha-subunit (Q49A, L95A, E96Q, I273M) or the replacement of Ser(59) in the beta-subunit enhanced the sensitivity to the inhibitor and resulted in a complete inhibition of the E. coli F(1)-ATPase by the plant-specific inhibitor tentoxin.

  12. Unidirectional rotary motion in achiral molecular motors.

    Science.gov (United States)

    Kistemaker, Jos C M; Štacko, Peter; Visser, Johan; Feringa, Ben L

    2015-11-01

    Control of the direction of motion is an essential feature of biological rotary motors and results from the intrinsic chirality of the amino acids from which the motors are made. In synthetic autonomous light-driven rotary motors, point chirality is transferred to helical chirality, and this governs their unidirectional rotation. However, achieving directional rotary motion in an achiral molecular system in an autonomous fashion remains a fundamental challenge. Here, we report an achiral molecular motor in which the presence of a pseudo-asymmetric carbon atom proved to be sufficient for exclusive autonomous disrotary motion of two appended rotor moieties. Isomerization around the two double bonds enables both rotors to move in the same direction with respect to their surroundings--like wheels on an axle--demonstrating that autonomous unidirectional rotary motion can be achieved in a symmetric system.

  13. Molecular Motor Proteins and Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Manal Farg

    2011-12-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder affecting motor neurons in the brain, brainstem and spinal cord, which is characterized by motor dysfunction, muscle dystrophy and progressive paralysis. Both inherited and sporadic forms of ALS share common pathological features, however, the initial trigger of neurodegeneration remains unknown. Motor neurons are uniquely targeted by ubiquitously expressed proteins in ALS but the reason for this selectively vulnerability is unclear. However motor neurons have unique characteristics such as very long axons, large cell bodies and high energetic metabolism, therefore placing high demands on cellular transport processes. Defects in cellular trafficking are now widely reported in ALS, including dysfunction to the molecular motors dynein and kinesin. Abnormalities to dynein in particular are linked to ALS, and defects in dynein-mediated axonal transport processes have been reported as one of the earliest pathologies in transgenic SOD1 mice. Furthermore, dynein is very highly expressed in neurons and neurons are particularly sensitive to dynein dysfunction. Hence, unravelling cellular transport processes mediated by molecular motor proteins may help shed light on motor neuron loss in ALS.

  14. Universal optimal working cycles of molecular motors.

    Science.gov (United States)

    Efremov, Artem; Wang, Zhisong

    2011-04-07

    Molecular motors capable of directional track-walking or rotation are abundant in living cells, and inspire the emerging field of artificial nanomotors. Some biomotors can convert 90% of free energy from chemical fuels into usable mechanical work, and the same motors still maintain a speed sufficient for cellular functions. This study exposed a new regime of universal optimization that amounts to a thermodynamically best working regime for molecular motors but is unfamiliar in macroscopic engines. For the ideal case of zero energy dissipation, the universally optimized working cycle for molecular motors is infinitely slow like Carnot cycle for heat engines. But when a small amount of energy dissipation reduces energy efficiency linearly from 100%, the speed is recovered exponentially due to Boltzmann's law. Experimental data on a major biomotor (kinesin) suggest that the regime of universal optimization has been largely approached in living cells, underpinning the extreme efficiency-speed trade-off in biomotors. The universal optimization and its practical approachability are unique thermodynamic advantages of molecular systems over macroscopic engines in facilitating motor functions. The findings have important implications for the natural evolution of biomotors as well as the development of artificial counterparts.

  15. Thermally driven molecular linear motors - A molecular dynamics study

    DEFF Research Database (Denmark)

    Zambrano, Harvey A; Walther, Jens Honore; Jaffe, Richard Lawrence

    2009-01-01

    We conduct molecular dynamics simulations of a molecular linear motor consisting of coaxial carbon nanotubes with a long outer carbon nanotube confining and guiding the motion of an inner short, capsule-like nanotube. The simulations indicate that the motion of the capsule can be controlled...

  16. Development of an electrically driven molecular motor.

    Science.gov (United States)

    Murphy, Colin J; Sykes, E Charles H

    2014-10-01

    For molecules to be used as components in molecular machinery, methods are required that couple individual molecules to external energy sources in order to selectively excite motion in a given direction. While significant progress has been made in the construction of synthetic molecular motors powered by light and by chemical reactions, there are few experimental examples of electrically driven molecular motors. To this end, we pioneered the use of a new, stable and tunable molecular rotor system based on surface-bound thioethers to comprehensively study many aspects of molecular rotation. As biological molecular motors often operate at interfaces, our synthetic system is especially amenable to microscopic interrogation as compared to solution-based systems. Using scanning tunneling microscopy (STM) and density functional theory, we studied the rotation of surface-bound thioethers, which can be induced either thermally or by electrons from the STM tip in a two-terminal setup. Moreover, the temperature and electron flux can be adjusted to allow each rotational event to be monitored at the molecular scale in real time. This work culminated in the first experimental demonstration of a single-molecule electric motor, where the electrically driven rotation of a butyl methyl sulfide molecule adsorbed on a copper surface could be directionally biased. The direction and rate of the rotation are related to the chirality of both the molecule and the STM tip (which serves as the electrode), illustrating the importance of the symmetry of the metal contacts in atomic-scale electrical devices. Copyright © 2014 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Cooperative transport by small teams of molecular motors

    OpenAIRE

    Klumpp, Stefan; Muller, Melanie J. I.; Lipowsky, Reinhard

    2006-01-01

    Molecular motors power directed transport of cargoes within cells. Even if a single motor is sufficient to transport a cargo, motors often cooperate in small teams. We discuss the cooperative cargo transport by several motors theoretically and explore some of its properties. In particular we emphasize how motor teams can drag cargoes through a viscous environment.

  18. Thermodynamics and kinetics of molecular motors.

    Science.gov (United States)

    Astumian, R Dean

    2010-06-02

    Molecular motors are first and foremost molecules, governed by the laws of chemistry rather than of mechanics. The dynamical behavior of motors based on chemical principles can be described as a random walk on a network of states. A key insight is that any molecular motor in solution explores all possible motions and configurations at thermodynamic equilibrium. By using input energy and chemical design to prevent motion that is not wanted, what is left behind is the motion that is desired. This review is focused on two-headed motors such as kinesin and Myosin V that move on a polymeric track. By use of microscopic reversibility, it is shown that the ratio between the number of forward steps and the number of backward steps in any sufficiently long time period does not directly depend on the mechanical properties of the linker between the two heads. Instead, this ratio is governed by the relative chemical specificity of the heads in the front-versus-rear position for the fuel, adenosine triphosphate and its products, adenosine diphosphate and inorganic phosphate. These insights have been key factors in the design of biologically inspired synthetic molecular walkers constructed out of DNA or out of small organic molecules.

  19. A model for processivity of molecular motors

    Institute of Scientific and Technical Information of China (English)

    Xie Ping; Dou Shuo-Xing; Wang Peng-Ye

    2004-01-01

    We propose a two-dimensional model for a complete description of the dynamics of molecular motors, including both the processive movement along track filaments and the dissociation from the filaments. Theoretical results on the distributions of the run length and dwell time at a given adenosine triphosphate (ATP) concentration, the dependences of mean run length, mean dwell time and mean velocity on ATP concentration and load are in good agreement with the previous experimental results.

  20. Exchangeability of the b subunit of the Cl(-)-translocating ATPase of Acetabularia acetabulum with the beta subunit of E. coli F1-ATPase: construction of the chimeric beta subunits and complementation studies.

    Science.gov (United States)

    Ikeda, M; Kadowaki, H; Ikeda, H; Moritani, C; Kanazawa, H

    1997-11-10

    The gene encoding the b subunit of the Cl(-)-translocating ATPase (aclB) was isolated from total RNA and poly(A)+ RNA of Acetabularia acetabulum and sequenced (total nucleotides of 3038 bp and an open reading frame with 478 amino acids). The deduced amino acid sequence showed high similarity to the beta subunit of the F type ATPases, but was different in the N-terminal 120 amino acids. The role of the N-terminal region was investigated using an F -ATPase beta-less mutant of E. coli, JP17. The JP17 strain expressing the aclB could not grow under conditions permitting oxidative phosphorylation, although ACLB was detected in the membrane fraction. The beta subunit was divided into three portions: amino acid position from 1 to 95 (portion A), 96 to 161 (portion B) and 162 to the C-terminus (portion C). The corresponding regions of ACLB were designated as portions A' (from 1 to 106), B' (from 107 to 172) and C' (from 173 to 478). Chimeric proteins with combinations of A-B'-C', A-B-C' and A'-B-C restored the function as the beta subunit in E. coli F0F1-complex, but those with combinations of A'-B'-C and A-B'-C had no function as the beta subunit. These findings suggested that portion B plays an important role in the assembly and function of the beta subunit in the F0F1-complex, while portion B' of ACLB exhibited inhibitory effects on assembly and function. In addition, portion A was also important for interaction of the beta subunit with the alpha subunit in E. coli F0F1-complex. These findings also suggested that the b subunit of the Cl(-)-translocating ATPase of A. acetabulum has a different function in the Cl(-)-translocating ATPase complex, although the primary structure resembled to the beta subunit of the F1-ATPase.

  1. Molecular genetics of distal hereditary motor neuropathies.

    Science.gov (United States)

    Irobi, Joy; De Jonghe, Peter; Timmerman, Vincent

    2004-10-01

    Inherited peripheral neuropathies comprise a wide variety of diseases primarily affecting the peripheral nervous system. The best-known peripheral neuropathy is Charcot-Marie-Tooth disease (CMT) described in 1886 by J.-M. Charcot, P. Marie and H.H. Tooth. In 1980, A.E. Harding and P.K. Thomas showed that in a large group of individuals with CMT, several only had motor abnormalities on clinical and electrophysiological examination, whereas sensory abnormalities were absent. This exclusively motor variant of CMT was designated as spinal CMT or hereditary distal spinal muscular atrophy, and included in the distal hereditary motor neuropathies (distal HMN). The distal HMN are clinically and genetically heterogeneous and are subdivided according to the mode of inheritance, age at onset and clinical evolution. Since the introduction of positional cloning, 12 chromosomal loci and seven disease-causing genes have been identified for autosomal dominant and recessive distal HMN. Most of the genes involved have housekeeping functions, as in RNA processing, translation synthesis, glycosylation, stress response, apoptosis, but also axonal trafficking and editing. Functional characterization of the mutations will help to unravel the cellular processes that underlie the specificity of motor neuropathies leading to neurogenic muscular atrophy of distal limb muscles. Here we review the recent progress of the molecular genetics of distal HMN and discuss the genes implicated.

  2. Light-driven rotary molecular motors : an ultrafast optical study

    NARCIS (Netherlands)

    Augulis, Ramunas; Klok, Martin; Loosdrecht, Paul H.M. van; Feringa, Bernard

    2009-01-01

    Molecular rotary motors, though common in nature, were first synthesized rather recently. One of the most promising categories of light-driven rotary molecular motors which allow for optical control is based on helical overcrowded alkenes. In this category of motors, the rotation of the motor’s roto

  3. Noninvasive probes of mitochondrial molecular motors

    Science.gov (United States)

    Nawarathna, Dharmakeerthna; Claycomb, James

    2005-03-01

    We report on a noninvasive method of probing mitochondrial molecular motors using nonlinear dielectric spectroscopy. It has been found previously that enzymes in the plasma membrane, particularly H+ ATPase, result in a strong low frequency (less than 100 Hz) nonlinear harmonic response. In this study, we find evidence that molecular motors located in the inner membranes of mitochondria cause the generation of harmonics at relatively high frequencies (1 - 30 kHz). In particular, we find that potassium cyanide (KCN), a respiratory inhibitor that binds to cytochrome c oxidase and thus prevents transport of protons across the mitochondrial inner membrane, suppresses the harmonic response. We observe this behavior in yeast (S. cerevisiae), a eucaryote that typically contains about 300 mitochondria, and B. indicas, a procaryote believed to be related to the ancient ancestor of mitochondria. Our current modeling efforts are focusing on a Brownian ratchet model of the F0 unit of ATP synthase, a remarkable molecular turbine driven by the proton gradient across the mitochondrial inner membrane.

  4. Stokes Efficiency of Molecular Motor-Cargo Systems

    Directory of Open Access Journals (Sweden)

    Hongyun Wang

    2008-01-01

    Full Text Available A molecular motor utilizes chemical free energy to generate a unidirectional motion through the viscous fluid. In many experimental settings and biological settings, a molecular motor is elastically linked to a cargo. The stochastic motion of a molecular motor-cargo system is governed by a set of Langevin equations, each corresponding to an individual chemical occupancy state. The change of chemical occupancy state is modeled by a continuous time discrete space Markov process. The probability density of a motor-cargo system is governed by a two-dimensional Fokker-Planck equation. The operation of a molecular motor is dominated by high viscous friction and large thermal fluctuations from surrounding fluid. The instantaneous velocity of a molecular motor is highly stochastic: the past velocity is quickly damped by the viscous friction and the new velocity is quickly excited by bombardments of surrounding fluid molecules. Thus, the theory for macroscopic motors should not be applied directly to molecular motors without close examination. In particular, a molecular motor behaves differently working against a viscous drag than working against a conservative force. The Stokes efficiency was introduced to measure how efficiently a motor uses chemical free energy to drive against viscous drag. For a motor without cargo, it was proved that the Stokes efficiency is bounded by 100% [H. Wang and G. Oster, (2002]. Here, we present a proof for the general motor-cargo system.

  5. Propagation Modeling and Analysis of Molecular Motors in Molecular Communication.

    Science.gov (United States)

    Chahibi, Youssef; Akyildiz, Ian F; Balasingham, Ilangko

    2016-12-01

    Molecular motor networks (MMNs) are networks constructed from molecular motors to enable nanomachines to perform coordinated tasks of sensing, computing, and actuation at the nano- and micro- scales. Living cells are naturally enabled with this same mechanism to establish point-to-point communication between different locations inside the cell. Similar to a railway system, the cytoplasm contains an intricate infrastructure of tracks, named microtubules, interconnecting different internal components of the cell. Motor proteins, such as kinesin and dynein, are able to travel along these tracks directionally, carrying with them large molecules that would otherwise be unreliably transported across the cytoplasm using free diffusion. Molecular communication has been previously proposed for the design and study of MMNs. However, the topological aspects of MMNs, including the effects of branches, have been ignored in the existing studies. In this paper, a physical end-to-end model for MMNs is developed, considering the location of the transmitter node, the network topology, and the receiver nodes. The end-to-end gain and group delay are considered as the performance measures, and analytical expressions for them are derived. The analytical model is validated by Monte-Carlo simulations and the performance of MMNs is analyzed numerically. It is shown that, depending on their nature and position, MMN nodes create impedance effects that are critical for the overall performance. This model could be applied to assist the design of artificial MMNs and to study cargo transport in neurofilaments to elucidate brain diseases related to microtubule jamming.

  6. Statistical kinetics of processive molecular motors

    Science.gov (United States)

    Schnitzer, Mark Jacob

    1999-10-01

    We describe new theoretical and experimental tools for studying biological motor proteins at the single molecule scale. These tools enable measurements of molecular fuel economies, thereby providing insight into the pathways for conversion of biochemical energy into mechanical work. Kinesin is an ATP-dependent motor that moves processively along microtubules in discrete steps of 8 nm. How many molecules of ATP are hydrolysed per step? To determine this coupling ratio, we develop a fluctuation analysis, which relates the variance in records of mechanical displacement to the number of rate-limiting biochemical transitions in the engine cycle. Using fluctuation analysis and optical trapping interferometry, we determine that near zero load, single molecules of kinesin hydrolyse one ATP nucleotide per 8-nm step. To study kinesin behavior under load, we use a molecular force clamp, capable of maintaining constant loads on single kinesin motors moving processively. Analysis of records of motion under variable ATP concentrations and loads reveals that kinesin is a `tightly- coupled' motor, maintaining the 1:1 coupling ratio up to loads of ~ 5 pN. Moreover, a Michaelis-Menten analysis of velocity shows that the kinesin cycle contains at least two load- dependent transitions. The rate of one of these transitions affects ATP affinity, while the other does not. Therefore, the kinesin stall force must depend on the ATP concentration, as is demonstrated experimentally. These findings rule out existing theoretical models of kinesin motility. We develop a simple theoretical formalism describing a tightly-coupled mechanism for movement. This `energy-landscape' formalism quantitatively accounts for motile properties of RNA polymerase (RNAP), the enzyme that transcribes DNA into RNA. The shapes of RNAP force-velocity curves indicate that biochemical steps limiting transcription rates at low loads do not generate movement. Modeling suggests that high loads may halt RNAP by promoting a

  7. Theoretical Analysis of Dynamic Processes for Interacting Molecular Motors.

    Science.gov (United States)

    Teimouri, Hamid; Kolomeisky, Anatoly B; Mehrabiani, Kareem

    2015-02-13

    Biological transport is supported by collective dynamics of enzymatic molecules that are called motor proteins or molecular motors. Experiments suggest that motor proteins interact locally via short-range potentials. We investigate the fundamental role of these interactions by analyzing a new class of totally asymmetric exclusion processes where interactions are accounted for in a thermodynamically consistent fashion. It allows us to connect explicitly microscopic features of motor proteins with their collective dynamic properties. Theoretical analysis that combines various mean-field calculations and computer simulations suggests that dynamic properties of molecular motors strongly depend on interactions, and correlations are stronger for interacting motor proteins. Surprisingly, it is found that there is an optimal strength of interactions (weak repulsion) that leads to a maximal particle flux. It is also argued that molecular motors transport is more sensitive to attractive interactions. Applications of these results for kinesin motor proteins are discussed.

  8. Thermodynamics and kinetics of a molecular motor ensemble.

    Science.gov (United States)

    Baker, J E; Thomas, D D

    2000-10-01

    If, contrary to conventional models of muscle, it is assumed that molecular forces equilibrate among rather than within molecular motors, an equation of state and an expression for energy output can be obtained for a near-equilibrium, coworking ensemble of molecular motors. These equations predict clear, testable relationships between motor structure, motor biochemistry, and ensemble motor function, and we discuss these relationships in the context of various experimental studies. In this model, net work by molecular motors is performed with the relaxation of a near-equilibrium intermediate step in a motor-catalyzed reaction. The free energy available for work is localized to this step, and the rate at which this free energy is transferred to work is accelerated by the free energy of a motor-catalyzed reaction. This thermodynamic model implicitly deals with a motile cell system as a dynamic network (not a rigid lattice) of molecular motors within which the mechanochemistry of one motor influences and is influenced by the mechanochemistry of other motors in the ensemble.

  9. Cytoskeleton Molecular Motors: Structures and Their Functions in Neuron.

    Science.gov (United States)

    Xiao, Qingpin; Hu, Xiaohui; Wei, Zhiyi; Tam, Kin Yip

    2016-01-01

    Cells make use of molecular motors to transport small molecules, macromolecules and cellular organelles to target region to execute biological functions, which is utmost important for polarized cells, such as neurons. In particular, cytoskeleton motors play fundamental roles in neuron polarization, extension, shape and neurotransmission. Cytoskeleton motors comprise of myosin, kinesin and cytoplasmic dynein. F-actin filaments act as myosin track, while kinesin and cytoplasmic dynein move on microtubules. Cytoskeleton motors work together to build a highly polarized and regulated system in neuronal cells via different molecular mechanisms and functional regulations. This review discusses the structures and working mechanisms of the cytoskeleton motors in neurons.

  10. Length regulation of active biopolymers by molecular motors.

    Science.gov (United States)

    Johann, Denis; Erlenkämper, Christoph; Kruse, Karsten

    2012-06-22

    For biopolymers like cytoskeletal actin filaments and microtubules, assembly and disassembly are inherently dissipative processes. Molecular motors can affect the rates of subunit removal at filament ends. We introduce a driven lattice-gas model to study the effects of motor-induced depolymerization on the length of active biopolymers and find that increasing motor activity sharpens unimodal steady-state length distributions. Furthermore, for sufficiently fast moving motors, the relative width of the length distribution is determined only by the attachment rate of motors. Our results show how established molecular processes can be used to robustly regulate the size of cytoskeletal structures like mitotic spindles.

  11. Distinct transport regimes for two elastically coupled molecular motors.

    Science.gov (United States)

    Berger, Florian; Keller, Corina; Klumpp, Stefan; Lipowsky, Reinhard

    2012-05-18

    Cooperative cargo transport by two molecular motors involves an elastic motor-motor coupling, which can reduce the motors' velocity and/or enhance their unbinding from the filament. We show theoretically that these interference effects lead, in general, to four distinct transport regimes. In addition to a weak coupling regime, kinesin and dynein motors are found to exhibit a strong coupling and an enhanced unbinding regime, whereas myosin motors are predicted to attain a reduced velocity regime. All of these regimes, which we derive by explicit calculations and general time scale arguments, can be explored experimentally by varying the elastic coupling strength.

  12. Unidirectional light-driven molecular motors based on overcrowded alkenes.

    Science.gov (United States)

    Cnossen, Arjen; Browne, Wesley R; Feringa, Ben L

    2014-01-01

    Over the last two decades, interest in nanotechnology has led to the design and synthesis of a toolbox of nanoscale versions of macroscopic devices and components. In molecular nanotechnology, linear motors based on rotaxanes and rotary motors based on overcrowded alkenes are particularly promising for performing work at the nanoscale. In this chapter, progress on light-driven molecular motors based on overcrowded alkenes is reviewed. Both the so-called first and second generation molecular motors are discussed, as well as their potential applications.

  13. Light-driven altitudinal molecular motors on surfaces

    NARCIS (Netherlands)

    London, Gabor; Carroll, Gregory T.; Fernández Landaluce, Tatiana; Pollard, Michael M.; Rudolf, Petra; Feringa, Ben L.

    2009-01-01

    A Cu(I)-catalyzed 1,3-dipolar cycloaddition was used to construct a monolayer of an altitudinal molecular motor on quartz and silicon substrates, which represents the fastest light-driven molecular motor, to date, grafted to a solid surface.

  14. Control of rotor function in light-driven molecular motors

    NARCIS (Netherlands)

    Lubbe, Anouk S.; Ruangsupapichat, Nopporn; Caroli, Giuseppe; Feringa, Ben L.

    2011-01-01

    A study is presented on the control of rotary motion of an appending rotor unit in a light-driven molecular motor. Two new light driven molecular motors were synthesized that contain aryl groups connected to the stereogenic centers. The aryl groups behave as bidirectional free rotors in three of the

  15. A General Random Walk Model of Molecular Motor

    Institute of Scientific and Technical Information of China (English)

    WANG Xian-Ju; AI Bao-Quan; LIU Guo-Tao; LIU Liang-Gang

    2003-01-01

    A general random walk model framework is presented which can be used to statistically describe the internaldynamics and external mechanical movement of molecular motors along filament track. The motion of molecular motorin a periodic potential and a constant force is considered. We show that the molecular motor's movement becomesslower with the potential barrier increasing, but if the forceis increased, the molecular motor's movement becomesfaster. The relation between the effective rate constant and the potential barrier's height, and that between the effectiverate constant and the value of the force are discussed. Our results are consistent with the experiments and relevanttheoretical consideration, and can be used to explain some physiological phenomena.

  16. Linking molecular motors to membrane cargo

    NARCIS (Netherlands)

    A.S. Akhmanova (Anna); J.A. Hammer (John)

    2010-01-01

    textabstractThree types of motors, myosins, kinesins, and cytoplasmic dynein, cooperate to transport intracellular membrane organelles. Transport of each cargo is determined by recruitment of specific sets of motors and their regulation. Targeting of motors to membranes often depends on the formatio

  17. Maximum power operation of interacting molecular motors

    DEFF Research Database (Denmark)

    Golubeva, Natalia; Imparato, Alberto

    2013-01-01

    We study the mechanical and thermodynamic properties of different traffic models for kinesin which are relevant in biological and experimental contexts. We find that motor-motor interactions play a fundamental role by enhancing the thermodynamic efficiency at maximum power of the motors......, as compared to the non-interacting system, in a wide range of biologically compatible scenarios. We furthermore consider the case where the motor-motor interaction directly affects the internal chemical cycle and investigate the effect on the system dynamics and thermodynamics....

  18. Motor proteins and molecular motors: how to operate machines at the nanoscale.

    Science.gov (United States)

    Kolomeisky, Anatoly B

    2013-11-20

    Several classes of biological molecules that transform chemical energy into mechanical work are known as motor proteins or molecular motors. These nanometer-sized machines operate in noisy stochastic isothermal environments, strongly supporting fundamental cellular processes such as the transfer of genetic information, transport, organization and functioning. In the past two decades motor proteins have become a subject of intense research efforts, aimed at uncovering the fundamental principles and mechanisms of molecular motor dynamics. In this review, we critically discuss recent progress in experimental and theoretical studies on motor proteins. Our focus is on analyzing fundamental concepts and ideas that have been utilized to explain the non-equilibrium nature and mechanisms of molecular motors.

  19. A General Random Walk Model of Molecular Motor

    Institute of Scientific and Technical Information of China (English)

    WANGXian-Ju; AIBao-Quan; LIUGuo-Tao; LIULiang-Gang

    2003-01-01

    A general random walk model framework is presented which can be used to statistically describe the internal dynamics and external mechanical movement of molecular motors along filament track. The motion of molecular motor in a periodic potential and a constant force is considered. We show that the molecular motor's movement becomes slower with the potential barrier increasing, but if the force is increased, the molecular motor''s movement becomes faster. The relation between the effective rate constant and the potential battler's height, and that between the effective rate constant and the value of the force are discussed. Our results are consistent with the experiments and relevant theoretical consideration, and can be used to explain some physiological phenomena.

  20. Collective alignment of polar filaments by molecular motors.

    Science.gov (United States)

    Ziebert, F; Vershinin, M; Gross, S P; Aranson, I S

    2009-04-01

    We study the alignment of polar biofilaments, such as microtubules and actin, subject to the action of multiple molecular motors attached simultaneously to more than one filament. Focusing on a paradigm model of only two filaments interacting with multiple motors, we were able to investigate in detail the alignment dynamics. While almost no alignment occurs in the case of a single motor, the filaments become rapidly aligned due to the collective action of the motors. Our analysis shows that the alignment time is governed by the number of bound motors and the magnitude of the motors' stepping fluctuations. We predict that the time scale of alignment is in the order of seconds, much faster than that reported for passive crosslink-induced bundling. In vitro experiments on the alignment of microtubules by multiple-motor covered beads are in qualitative agreement. We also discuss another mode of fast alignment of filaments, namely the cooperation between motors and passive crosslinks.

  1. Exploiting molecular motors as nanomachines: the mechanisms of de novo and re-engineered cytoskeletal motors.

    Science.gov (United States)

    DelRosso, Nicole V; Derr, Nathan D

    2017-01-11

    Cytoskeletal molecular motors provide exciting proof that nanoscale transporters can be highly efficient, moving for microns along filamentous tracks by hydrolyzing ATP to fuel nanometer-size steps. For nanotechnology, such conversion of chemical energy into productive work serves as an enticing platform for re-purposing and re-engineering. It also provides a roadmap for successful molecular mechanisms that can be mimicked to create de novo molecular motors for nanotechnology applications. Here we focus specifically on how the mechanisms of molecular motors are being re-engineered for greater control over their transport parameters. We then discuss mechanistic work to create fully synthetic motors de novo and conclude with future directions in creating novel motor systems.

  2. The Art of Building Small : From Molecular Switches to Molecular Motors

    NARCIS (Netherlands)

    Feringa, Bernard

    2007-01-01

    Molecular switches and motors are essential components of artificial molecular machines. In this perspective, we discuss progress in our design, synthesis, and functioning of photochemical and electrochemical switches and chemical and light-driven molecular motors. Special emphasis is given to the c

  3. The art of building small : From molecular switches to molecular motors

    NARCIS (Netherlands)

    Feringa, Ben L.

    2007-01-01

    Molecular switches and motors are essential components of artificial molecular machines. In this perspective, we discuss progress in our design, synthesis, and functioning of photochemical and electrochemical switches and chemical and light-driven molecular motors. Special emphasis is given to the c

  4. The art of building small : From molecular switches to molecular motors

    NARCIS (Netherlands)

    Feringa, Ben L.

    2007-01-01

    Molecular switches and motors are essential components of artificial molecular machines. In this perspective, we discuss progress in our design, synthesis, and functioning of photochemical and electrochemical switches and chemical and light-driven molecular motors. Special emphasis is given to the

  5. The Art of Building Small : From Molecular Switches to Molecular Motors

    NARCIS (Netherlands)

    Feringa, Bernard

    2007-01-01

    Molecular switches and motors are essential components of artificial molecular machines. In this perspective, we discuss progress in our design, synthesis, and functioning of photochemical and electrochemical switches and chemical and light-driven molecular motors. Special emphasis is given to the

  6. Monte Carlo simulations of single and coupled synthetic molecular motors.

    Science.gov (United States)

    Chen, C-M; Zuckermann, M

    2012-11-01

    We use a minimal model to study the processive motion of coupled synthetic molecular motors along a DNA track and we present data from Monte Carlo (MC) computer simulations based on this model. The model was originally proposed by Bromley et al. [HFSP J. 3, 204 (2009)] for studying the properties of a synthetic protein motor, the "Tumbleweed" (TW), and involves rigid Y-shaped motors diffusively rotating along the track while controlled by a series of periodically injected ligand pulses into the solution. The advantage of the model is that it mimics the mechanical properties of the TW motor in detail. Both the average first passage time which measures the diffusive motion of the motors, and the average dwell time on the track which measures their processivity are investigated by varying the parameters of the model. The latter includes ligand concentration and the range and strength of the binding interaction between motors and the track. In particular, it is of experimental interest to study the dependence of these dynamic time scales of the motors on the ligand concentration. Single rigid TW motors were first studied since no previous MC simulations of these motors have been performed. We first studied single motors for which we found a logarithmic decrease of the average first passage time and a logarithmic increase of the average dwell time with increasing ligand concentration. For two coupled motors, the dependence on ligand concentration is still logarithmic for the average first passage time but becomes linear for the average dwell time. This suggests a much greater stability in the processive motion of coupled motors as compared to single motors in the limit of large ligand concentration. By increasing the number of coupled motors, m, it was found that the average first passage time of the coupled motors only increases slowly with m while the average dwell time increases exponentially with m. Thus the stability of coupled motors on the track can be

  7. Ultrafast ignition of a uni-directional molecular motor

    Directory of Open Access Journals (Sweden)

    Feringa Ben L.

    2013-03-01

    Full Text Available Light-driven molecular motors convert light into mechanical energy via excited state reactions. In this work we follow sub-picosecond primary events in the cycle of a two-stroke unidirectional motor by fluorescence up-conversion and transient absorption.

  8. Unidirectional Light-Driven Molecular Motors Based on Overcrowded Alkenes

    NARCIS (Netherlands)

    Cnossen, Arjen; Browne, Wesley R.; Feringa, Ben L.; Credi, Alberto; Silvi, Serena; Venturi, Margherita

    2014-01-01

    Over the last two decades, interest in nanotechnology has led to the design and synthesis of a toolbox of nanoscale versions of macroscopic devices and components. In molecular nanotechnology, linear motors based on rotaxanes and rotary motors based on overcrowded alkenes are particularly promising

  9. Light-Driven Rotary Molecular Motors on Gold Nanoparticles

    NARCIS (Netherlands)

    Pollard, Michael M.; ter Wiel, Matthijs K. J.; van Delden, Richard A.; Vicario, Javier; Koumura, Nagatoshi; van den Brom, Coenraad R.; Meetsma, Auke; Feringa, Ben L.

    2008-01-01

    We report the synthesis of unidirectional light-driven rotary molecular motors based oil chiral overcrowded alkenes and their immobilisation on the surface of gold nanoparticles through two anchors. Using a combination of (1)H and (13)C NMR, UV/Vis and CD spectroscopy, we show that these motors pres

  10. Rotation of artificial rotor axles in rotary molecular motors

    National Research Council Canada - National Science Library

    Baba, Mihori; Iwamoto, Kousuke; Iino, Ryota; Ueno, Hiroshi; Hara, Mayu; Nakanishi, Atsuko; Kishikawa, Jun-ichi; Noji, Hiroyuki; Yokoyama, Ken

    2016-01-01

    [F.sub.1]- and [V.sub.1]-ATPase are rotary molecular motors that convert chemical energy released upon ATP hydrolysis into torque to rotate a central rotor axle against the surrounding catalytic stator cylinder with high efficiency...

  11. Fluctuation theorem for the flashing ratchet model of molecular motors

    Science.gov (United States)

    Lacoste, D.; Mallick, K.

    2009-08-01

    Molecular motors convert chemical energy derived from the hydrolysis of adenosine triphosphate (ATP) into mechanical energy. A well-studied model of a molecular motor is the flashing ratchet model. We show that this model exhibits a fluctuation relation known as the Gallavotti-Cohen symmetry. Our study highlights the fact that the symmetry is present only if the chemical and mechanical degrees of freedom are both included in the description.

  12. Molecular motor traffic: From biological nanomachines to macroscopic transport

    Science.gov (United States)

    Lipowsky, Reinhard; Chai, Yan; Klumpp, Stefan; Liepelt, Steffen; Müller, Melanie J. I.

    2006-12-01

    All cells of animals and plants contain complex transport systems based on molecular motors which walk along cytoskeletal filaments. These motors are rather small and have a size of 20-100 nm but are able to pull vesicles, organelles and other types of cargo over large distances, from micrometers up to meters. There are several families of motors: kinesins, dyneins, and myosins. Most of these motors have two heads which are used as legs and perform discrete steps along the filaments. Several aspects of the motor behavior will be discussed: motor cycles of two-headed motors; walks of single motors or cargo particles which consist of directed movements interrupted by random, diffusive motion; cargo transport through tube-like compartments; active diffusion of cargo particles in slab-like compartments; cooperative transport of cargo by several motors which may be uni- or bi-directional; and systems with many interacting motors that exhibit traffic jams, self-organized density and flux patterns, and traffic phase transitions far from equilibrium. It is necessary to understand these traffic phenomena in a quantitative manner in order to construct and optimize biomimetic transport systems based on motors and filaments with many possible applications in bioengineering, pharmacology, and medicine.

  13. Towards synthetic molecular motors: a model elastic-network study

    Science.gov (United States)

    Sarkar, Amartya; Flechsig, Holger; Mikhailov, Alexander S.

    2016-04-01

    Protein molecular motors play a fundamental role in biological cells and development of their synthetic counterparts is a major challenge. Here, we show how a model motor system with the operation mechanism resembling that of muscle myosin can be designed at the concept level, without addressing the implementation aspects. The model is constructed as an elastic network, similar to the coarse-grained descriptions used for real proteins. We show by numerical simulations that the designed synthetic motor can operate as a deterministic or Brownian ratchet and that there is a continuous transition between such two regimes. The motor operation under external load, approaching the stall condition, is also analysed.

  14. Crowding of molecular motors determines microtubule depolymerization

    CERN Document Server

    Reese, Louis; Frey, Erwin

    2011-01-01

    Assembly and disassembly dynamics of microtubules (MTs) is tightly controlled by MT associated proteins. Here, we investigate how plus-end-directed depolymerases of the kinesin-8 family regulate MT depolymerization dynamics. Employing an individual-based model, we reproduce experimental findings. Moreover, crowding is identified as the key regulatory mechanism of depolymerization dynamics. Our analysis gives two qualitatively distinct regimes. For motor densities above a particular threshold, a macroscopic traffic jam emerges at the plus-end and the MT dynamics become independent of the motor concentration. Below this threshold, microscopic traffic jams at the tip arise which cancel out the effect of the depolymerization kinetics such that the depolymerization speed is solely determined by the motor density. Because this density changes over the MT length, length-dependent regulation is possible. Remarkably, motor cooperativity does not affect the depolymerization speed but only the end-residence time of depo...

  15. Cooperative behavior of molecular motors: Cargo transport and traffic phenomena

    Science.gov (United States)

    Lipowsky, Reinhard; Beeg, Janina; Dimova, Rumiana; Klumpp, Stefan; Müller, Melanie J. I.

    2010-01-01

    All eukaryotic cells including those of our own body contain complex transport systems based on molecular motors which walk along cytoskeletal filaments. These motors are rather small and make discrete mechanical steps with a step size of the order of 10 nm but are able to pull cargo particles over much larger distances, from micrometers up to meters. In vivo, the intracellular cargos include large membrane-bounded organelles, smaller vesicles, a subset of mRNAs, cytoskeletal filaments, and various protein building blocks, which are transported between different cell compartments. This cargo transport is usually performed by teams of motors. If all motors belong to the same molecular species, the cooperative action of the motors leads to uni-directional transport with a strongly increased run length and with a characteristic force dependence of the velocity distributions. If two antagonistic teams of motors pull on the same cargo particle, they perform a stochastic tug-of-war, which is characterized by a subtle force balance between the two motor teams and leads to several distinct patterns of bi-directional transport. So far, all experimental observations on bi-directional transport are consistent with such a tug-of-war. If many motors and/or cargo particles are transported along the filaments, one encounters various traffic phenomena. Depending on their mutual interactions and the compartment geometry, the motors form various spatio-temporal patterns such as traffic jams, and undergo nonequilibrium phase transitions between different patterns of transport.

  16. Control of rotor motion in a light-driven molecular motor : Towards a molecular gearbox

    NARCIS (Netherlands)

    Wiel, Matthijs K.J. ter; Delden, Richard A. van; Meetsma, Auke; Feringa, Bernard

    2005-01-01

    Controlled intramolecular movement and coupling of motor and rotor functions is exerted by this new molecular device. The rate of rotation of the rotor part of the molecule can be adjusted by alteration of the conformation of the motor part of the molecule. For all states of the motor part, differen

  17. Tetrapodal molecular switches and motors: synthesis and photochemistry.

    Science.gov (United States)

    Chen, Kuang-Yen; Wezenberg, Sander J; Carroll, Gregory T; London, Gábor; Kistemaker, Jos C M; Pijper, Thomas C; Feringa, Ben L

    2014-08-01

    The design, synthesis, and dynamic behavior of a series of novel tetrapodal molecular switches and motors containing common functional groups for attachment to various inorganic and organic surfaces are presented. Using a Diels-Alder reaction, an anthracene unit with four functionalized alkyl substituents ("legs") was coupled to maleimide-functionalized molecular switches or motors under ambient conditions. Terminal functional groups at the "legs" include thioacetates and azides, making these switches and motors ideal candidates for attachment to metallic or alkyne-functionalized surfaces. UV/vis absorption spectroscopy shows that the molecular switches and motors retain their ability to undergo reversible photoinduced and/or thermally induced structural changes after attachment to the tetrapodal anthracene.

  18. A Stochastic Markov Model for Coordinated Molecular Motors

    CERN Document Server

    Materassi, Donatello; Salapaka, Murti V

    2010-01-01

    Many cell functions are accomplished thanks to intracellular transport mechanisms of macromolecules along filaments. Molecular motors such as dynein or kinesin are proteins playing a primary role in these processes. The behavior of such proteins is quite well understood when there is only one of them moving a cargo particle. Indeed, numerous in vitro experiments have been performed to derive accurate models for a single molecular motor. However, in vivo macromolecules are often carried by multiple motors. The main focus of this paper is to provide an analysis of the behavior of more molecular motors interacting together in order to improve the understanding of their actual physiological behavior. Previous studies provide analyses based on results obtained from Monte Carlo simulations. Different from these studies, we derive an equipollent probabilistic model to describe the dynamics of multiple proteins coupled together and provide an exact theoretical analysis. We are capable of obtaining the probability den...

  19. Molecular motor transport through hollow nanowires

    DEFF Research Database (Denmark)

    Lard, Mercy; Ten Siethoff, Lasse; Generosi, Johanna;

    2014-01-01

    Biomolecular motors offer self-propelled, directed transport in designed microscale networks and can potentially replace pump-driven nanofluidics. However, in existing systems, transportation is limited to the two-dimensional plane. Here we demonstrate fully one-dimensional (1D) myosin-driven mot......Biomolecular motors offer self-propelled, directed transport in designed microscale networks and can potentially replace pump-driven nanofluidics. However, in existing systems, transportation is limited to the two-dimensional plane. Here we demonstrate fully one-dimensional (1D) myosin......-driven motion of fluorescent probes (actin filaments) through 80 nm wide, Al2O 3 hollow nanowires of micrometer length. The motor-driven transport is orders of magnitude faster than would be possible by passive diffusion. The system represents a necessary element for advanced devices based on gliding assays...

  20. Chemically Optimizing Operational Efficiency of Molecular Rotary Motors

    NARCIS (Netherlands)

    Conyard, Jamie; Cnossen, Arjen; Browne, Wesley R.; Feringa, Ben L.; Meech, Stephen R.

    2014-01-01

    Unidirectional molecular rotary motors that harness photoinduced cis-trans (E-Z) isomerization are promising tools for the conversion of light energy to mechanical motion in nanoscale molecular machines. Considerable progress has been made in optimizing the frequency of ground-state rotation, but le

  1. Synthetic light-activated molecular switches and motors on surfaces

    NARCIS (Netherlands)

    Katsonis, Nathalie; Lubomska, Monika; Pollard, Michael M.; Feringa, Ben L.; Rudolf, Petra

    2007-01-01

    Recent advances in synthetic methods and analysis techniques provide a basis for the construction and characterization of organized arrays of molecular switches and motors on surfaces. Among them, molecular systems that can be controlled by light are particularly promising because of their ease of a

  2. Engineering controllable bidirectional molecular motors based on myosin.

    Science.gov (United States)

    Chen, Lu; Nakamura, Muneaki; Schindler, Tony D; Parker, David; Bryant, Zev

    2012-02-19

    Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells and have potential applications in molecular detection and diagnostic devices. Engineering molecular motors with controllable properties will allow selective perturbation of mechanical processes in living cells and provide optimized device components for tasks such as molecular sorting and directed assembly. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions and other signals. Here, we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies and guided by a structural model for the redirected power stroke of myosin VI, we have constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should make it possible to achieve spatiotemporal control over a range of motor properties including processivity, stride size and branchpoint turning.

  3. Embedding dual function into molecular motors through collective motion.

    Science.gov (United States)

    Saito, Nen; Kaneko, Kunihiko

    2017-03-10

    Protein motors, such as kinesins and dyneins, bind to a microtubule and travel along it in a specific direction. Previously, it was thought that the directionality for a given motor was constant in the absence of an external force. However, the directionality of the kinesin-5 Cin8 was recently found to change as the number of motors that bind to the same microtubule is increased. Here, we introduce a simple mechanical model of a microtubule-sliding assay in which multiple motors interact with the filament. We show that, due to the collective phenomenon, the directionality of the motor changes (e.g., from minus- to plus- end directionality), depending on the number of motors. This is induced by a large diffusive component in the directional walk and by the subsequent frustrated motor configuration, in which multiple motors pull the filament in opposite directions, similar to a game of tug-of-war. A possible role of the dual-directional motors for the mitotic spindle formation is also discussed. Our framework provides a general mechanism to embed two conflicting tasks into a single molecular machine, which works context-dependently.

  4. Stochastic simulations of cargo transport by processive molecular motors.

    Science.gov (United States)

    Korn, Christian B; Klumpp, Stefan; Lipowsky, Reinhard; Schwarz, Ulrich S

    2009-12-28

    We use stochastic computer simulations to study the transport of a spherical cargo particle along a microtubule-like track on a planar substrate by several kinesin-like processive motors. Our newly developed adhesive motor dynamics algorithm combines the numerical integration of a Langevin equation for the motion of a sphere with kinetic rules for the molecular motors. The Langevin part includes diffusive motion, the action of the pulling motors, and hydrodynamic interactions between sphere and wall. The kinetic rules for the motors include binding to and unbinding from the filament as well as active motor steps. We find that the simulated mean transport length increases exponentially with the number of bound motors, in good agreement with earlier results. The number of motors in binding range to the motor track fluctuates in time with a Poissonian distribution, both for springs and cables being used as models for the linker mechanics. Cooperativity in the sense of equal load sharing only occurs for high values for viscosity and attachment time.

  5. Single rotating molecule-machines: nanovehicles and molecular motors.

    Science.gov (United States)

    Rapenne, Gwénaël; Joachim, Christian

    2014-01-01

    In the last decade many molecular machines with controlled molecular motions have been synthesized. In the present review chapter we will present and discuss our contribution to the field, in particular through some examples of rotating molecular machines that have been designed, synthesized, and studied in our group. After starting by explaining why it is so important to study such machines as single molecules, we will focus on two families of molecular machines, nanovehicles and molecular motors. The first members of the nanovehicle family are molecules with two triptycenes as wheels: the axle and the wheelbarrow. Then come the four-wheel nanocars. Since triptycene wheels are not very mobile on metallic surfaces, alternative wheels with a bowl-shape structure have also been synthesized and studied on surfaces. The molecular motors are built around ruthenium organometallic centers and have a piano-stool geometry with peripheric ferrocenyl groups.

  6. Controlled Rotation and Manipulation of Individual Molecular Motors

    Science.gov (United States)

    Kersell, Heath; Perera, U. G. E.; Ample, F.; Zhang, Y.; Vives, G.; Echeverria, J.; Grisolia, M.; Rapenne, G.; Joachim, C.; Hla, S.-W.

    2015-03-01

    The design of artificial molecular machines often takes inspiration from macroscopic machines, but the parallels between the two are frequently only superficial because many molecular machines are governed by quantum processes. Previously, chemically and light driven rotary molecular motors have been developed. For electrically driven motors, tunneling electrons from the tip of a scanning tunneling microscope (STM) have been used to drive rotation in a simple rotor into a single direction and to move a wheeled molecule across a surface. Here, we show that a single standalone molecular motor adsorbed on a gold surface can be made to rotate in a clockwise or counterclockwise direction [1] by selective inelastic electron tunneling through different sub-units of the motor. Our motor is composed of a tripodal stator for vertical positioning, a five-arm rotator for controlled rotations, and a Ru atomic ball bearing connecting the static and rotational parts. The directional rotation originates from saw-tooth-like rotational potentials, which are determined by the internal molecular structure and are independent of the surface adsorption site. This project is supported by the US DOE, BES grant: DE-FG02-02ER46012.

  7. Energetics and efficiency of a molecular motor model

    DEFF Research Database (Denmark)

    C. Fogedby, Hans; Svane, Axel

    2013-01-01

    The energetics and efficiency of a linear molecular motor model proposed by Mogilner et al. (Phys. Lett. 237, 297 (1998)) is analyzed from an analytical point of view. The model which is based on protein friction with a track is described by coupled Langevin equations for the motion in combination...... with coupled master equations for the ATP hydrolysis. Here the energetics and efficiency of the motor is addressed using a many body scheme with focus on the efficiency at maximum power (EMP). It is found that the EMP is reduced from about 10 pct in a heuristic description of the motor to about 1 per mille...... when incorporating the full motor dynamics, owing to the strong dissipation associated with the motor action....

  8. Biasing the random walk of a molecular motor

    Energy Technology Data Exchange (ETDEWEB)

    Astumian, R Dean [Department of Physics, University of Maine, Orono, ME 04469-5709 (United States)

    2005-11-30

    Biomolecular motors are often described in mechanical terms, with analogy to cars, turbines, judo throws, levers, etc. It is important to remember however that because of their small size, and because of the aqueous environment in which molecular motors move, viscous drag and thermal noise dominate the inertial forces that drive macroscopic machines. The sequence of motions-conformational changes-by which a motor protein moves can best be described as a random walk, with transitions from one state to another occurring by thermal activation over energy barriers. In this paper I will address the question of how this random walk is biased by a non-equilibrium chemical reaction (ATP hydrolysis) so that the motor molecule moves preferentially (with almost unit certainty) in one direction, even when an external force is applied to drive it in the opposite direction. I will also discuss how these 'soft matter' motors can achieve thermodynamic efficiencies of nearly 100%.

  9. Stochastic modeling of cargo transport by teams of molecular motors

    CERN Document Server

    Klein, Sarah; Santen, Ludger

    2014-01-01

    Many different types of cellular cargos are transported bidirectionally along microtubules by teams of molecular motors. The motion of this cargo-motors system has been experimentally characterized in vivo as processive with rather persistent directionality. Different theoretical approaches have been suggested in order to explore the origin of this kind of motion. An effective theoretical approach, introduced by M\\"uller et al., describes the cargo dynamics as a tug-of-war between different kinds of motors. An alternative approach has been suggested recently by Kunwar et al., who considered the coupling between motor and cargo in more detail. Based on this framework we introduce a model considering single motor positions which we propagate in continuous time. Furthermore, we analyze the possible influence of the discrete time update schemes used in previous publications on the system's dynamic.

  10. Traffic of molecular motors: from theory to experiments

    CERN Document Server

    Pierobon, Paolo

    2007-01-01

    Intracellular transport along microtubules or actin filaments, powered by molecular motors such as kinesins, dyneins or myosins, has been recently modeled using one-dimensional driven lattice gases. We discuss some generalizations of these models, that include extended particles and defects. We investigate the feasibility of single molecule experiments aiming to measure the average motor density and to locate the position of traffic jams by mean of a tracer particle. Finally, we comment on preliminary single molecule experiments performed in living cells.

  11. Symposium FF: Molecular Motors, Nanomachines, and Active Nanostructures

    Science.gov (United States)

    2008-06-23

    long and thin tubal heart called “dorsal vessel DV.” Lepidoptera larvae, Ctenoplusia agnata were used in this study. Resulting from culture examinations...motors. It is difficult to systematically vary parameters in studies of biological molecular motors and using a model system can help understand the...were generated by systematically varying the conditions of assembly: (1) mobile linear composites, (2) rotating circular composites, and (3) immobile

  12. Coiled coils and SAH domains in cytoskeletal molecular motors.

    Science.gov (United States)

    Peckham, Michelle

    2011-10-01

    Cytoskeletal motors include myosins, kinesins and dyneins. Myosins move along tracks of actin filaments, whereas kinesins and dyneins move along microtubules. Many of these motors are involved in trafficking cargo in cells. However, myosins are mostly monomeric, whereas kinesins are mostly dimeric, owing to the presence of a coiled coil. Some myosins (myosins 6, 7 and 10) contain an SAH (single α-helical) domain, which was originally thought to be a coiled coil. These myosins are now known to be monomers, not dimers. The differences between SAH domains and coiled coils are described and the potential roles of SAH domains in molecular motors are discussed.

  13. Molecular motor assembly of a biomimetic system

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Active biological molecules and functional structures can be fabricated into a bio-mimetic system by using molecular assembly method. Such materials can be used for the drug delivery, disease diagnosis and therapy, and new nanodevice construction.

  14. Collective transport of weakly interacting molecular motors with Langmuir kinetics

    Science.gov (United States)

    Chandel, Sameep; Chaudhuri, Abhishek; Muhuri, Sudipto

    2015-04-01

    Filament-based intracellular transport involves the collective action of molecular motor proteins. Experimental evidences suggest that microtubule (MT) filament bound motor proteins such as kinesins weakly interact among themselves during transport and with the surrounding cellular environment. Motivated by these observations we study a driven lattice gas model for collective unidirectional transport of molecular motors on open filament. This model incorporates short-range next-nearest-neighbour (NNN) interactions between the motors and couples the transport process on filament with surrounding cellular environment through adsorption-desorption Langmuir kinetics (LK) of the motors. We analyse this model within the framework of a mean-field (MF) theory in the limit of weak interactions between the motors. We point to the mapping of this model with the non-conserved version of the Katz-Lebowitz-Spohn (KLS) model. The system exhibits rich phase behavior with a variety of inhomogeneous phases including localized shocks in the bulk of the filament. We obtain the steady-state density and current profiles, analyse their variation as a function of the strength of interaction and construct the non-equilibrium MF phase diagram. We compare these MF results with Monte Carlo simulations and find that the MF analysis shows reasonably good agreement with simulation results as long as the motors are weakly interacting. For sufficently strong NNN interaction between the motors, the mean-field results deviate significantly, and for very strong NNN interaction in the absence of LK, the current in the lattice is determined solely by the NNN interaction parameter and it becomes independent of entry and exit rates of motors at the filament boundaries.

  15. "Cargo-mooring" as an operating principle for molecular motors.

    Science.gov (United States)

    Lisowski, Bartosz; Kuśmierz, Łukasz; Żabicki, Michał; Bier, Martin

    2015-06-07

    Navigating through an ever-changing and unsteady environment, and utilizing chemical energy, molecular motors transport the cell׳s crucial components, such as organelles and vesicles filled with neurotransmitter. They generate force and pull cargo, as they literally walk along the polymeric tracks, e.g. microtubules. What we suggest in this paper is that the motor protein is not really pulling its load. The load is subject to diffusion and the motor may be doing little else than rectifying the fluctuations, i.e. ratcheting the load׳s diffusion. Below we present a detailed model to show how such ratcheting can quantitatively account for observed data. The consequence of such a mechanism is the dependence of the transport׳s speed and efficacy not only on the motor, but also on the cargo (especially its size) and on the environment (i.e. its viscosity and structure). Current experimental works rarely provide this type of information for in vivo studies. We suggest that even small differences between assays can impact the outcome. Our results agree with those obtained in wet laboratories and provide novel insight in a molecular motor׳s functioning.

  16. Patterns of molecular motors that guide and sort filaments.

    Science.gov (United States)

    Rupp, Beat; Nédélec, François

    2012-11-21

    Molecular motors can be immobilized to transport filaments and loads that are attached to these filaments inside a nano-device. However, if motors are distributed uniformly over a flat surface, the motility is undirected, and the filaments move equally in all directions. For many applications it is important to control the direction in which the filaments move, and two strategies have been explored to achieve this: applying external forces and confining the filaments inside channels. In this article, we discuss a third strategy in which the topography of the sample remains flat, but the motors are distributed non-uniformly over the surface. Systems of filaments and patterned molecular motors were simulated using a stochastic engine that included Brownian motion and filament bending elasticity. Using an evolutionary algorithm, patterns were optimized for their capacity to precisely control the paths of the filaments. We identified patterns of motors that could either direct the filaments in a particular direction, or separate short and long filaments. These functionalities already exceed what has been achieved with confinement. The patterns are composed of one or two types of motors positioned in lines or along arcs and should be easy to manufacture. Finally, these patterns can be easily combined into larger designs, allowing one to precisely control the motion of microscopic objects inside a device.

  17. Amino acid sequence of the oligomycin sensitivity-conferring protein (OSCP) of beef-heart mitochondria and its homology with the delta-subunit of the F1-ATPase of Escherichia coli.

    Science.gov (United States)

    Ovchinnikov, Y A; Modyanov, N N; Grinkevich, V A; Aldanova, N A; Trubetskaya, O E; Nazimov, I V; Hundal, T; Ernster, L

    1984-01-23

    The complete amino acid sequence of the oligomycin sensitivity-conferring protein (OSCP) of beef-heart mitochondria is reported. The protein contains 190 amino acids and has a molecular mass of 20 967. Its structure is characterized by a concentration of charged amino acids in the two terminal segments (N 1-77 and C 128-190) of the protein, whereas its central region is more hydrophobic. The earlier reported homology of the protein with the delta-subunit of E. coli F1, based on the terminal amino acid sequences of OSCP, is further substantiated.

  18. In Control of Motion : From Molecular Switches to Molecular Motors

    NARCIS (Netherlands)

    Feringa, Bernard

    2001-01-01

    The design of molecular systems in which controlled linear and rotary motion can be achieved under the influence of an external signal is a major endeavor toward future nanoscale machinery. In this Account we describe the development of molecular switches and the discoveries that culminated in the

  19. Rotation of artificial rotor axles in rotary molecular motors.

    Science.gov (United States)

    Baba, Mihori; Iwamoto, Kousuke; Iino, Ryota; Ueno, Hiroshi; Hara, Mayu; Nakanishi, Atsuko; Kishikawa, Jun-Ichi; Noji, Hiroyuki; Yokoyama, Ken

    2016-10-04

    F1- and V1-ATPase are rotary molecular motors that convert chemical energy released upon ATP hydrolysis into torque to rotate a central rotor axle against the surrounding catalytic stator cylinder with high efficiency. How conformational change occurring in the stator is coupled to the rotary motion of the axle is the key unknown in the mechanism of rotary motors. Here, we generated chimeric motor proteins by inserting an exogenous rod protein, FliJ, into the stator ring of F1 or of V1 and tested the rotation properties of these chimeric motors. Both motors showed unidirectional and continuous rotation, despite no obvious homology in amino acid sequence between FliJ and the intrinsic rotor subunit of F1 or V1 These results showed that any residue-specific interactions between the stator and rotor are not a prerequisite for unidirectional rotation of both F1 and V1 The torque of chimeric motors estimated from viscous friction of the rotation probe against medium revealed that whereas the F1-FliJ chimera generates only 10% of WT F1, the V1-FliJ chimera generates torque comparable to that of V1 with the native axle protein that is structurally more similar to FliJ than the native rotor of F1 This suggests that the gross structural mismatch hinders smooth rotation of FliJ accompanied with the stator ring of F1.

  20. Myosin-I molecular motors at a glance.

    Science.gov (United States)

    McIntosh, Betsy B; Ostap, E Michael

    2016-07-15

    Myosin-I molecular motors are proposed to play various cellular roles related to membrane dynamics and trafficking. In this Cell Science at a Glance article and the accompanying poster, we review and illustrate the proposed cellular functions of metazoan myosin-I molecular motors by examining the structural, biochemical, mechanical and cell biological evidence for their proposed molecular roles. We highlight evidence for the roles of myosin-I isoforms in regulating membrane tension and actin architecture, powering plasma membrane and organelle deformation, participating in membrane trafficking, and functioning as a tension-sensitive dock or tether. Collectively, myosin-I motors have been implicated in increasingly complex cellular phenomena, yet how a single isoform accomplishes multiple types of molecular functions is still an active area of investigation. To fully understand the underlying physiology, it is now essential to piece together different approaches of biological investigation. This article will appeal to investigators who study immunology, metabolic diseases, endosomal trafficking, cell motility, cancer and kidney disease, and to those who are interested in how cellular membranes are coupled to the underlying actin cytoskeleton in a variety of different applications.

  1. Interferometric Scattering Microscopy for the Study of Molecular Motors.

    Science.gov (United States)

    Andrecka, J; Takagi, Y; Mickolajczyk, K J; Lippert, L G; Sellers, J R; Hancock, W O; Goldman, Y E; Kukura, P

    2016-01-01

    Our understanding of molecular motor function has been greatly improved by the development of imaging modalities, which enable real-time observation of their motion at the single-molecule level. Here, we describe the use of a new method, interferometric scattering microscopy, for the investigation of motor protein dynamics by attaching and tracking the motion of metallic nanoparticle labels as small as 20nm diameter. Using myosin-5, kinesin-1, and dynein as examples, we describe the basic assays, labeling strategies, and principles of data analysis. Our approach is relevant not only for motor protein dynamics but also provides a general tool for single-particle tracking with high spatiotemporal precision, which overcomes the limitations of single-molecule fluorescence methods.

  2. Universal bound on the efficiency of molecular motors

    Science.gov (United States)

    Pietzonka, Patrick; Barato, Andre C.; Seifert, Udo

    2016-12-01

    The thermodynamic uncertainty relation provides an inequality relating any mean current, the associated dispersion and the entropy production rate for arbitrary non-equilibrium steady states. Applying it here to a general model of a molecular motor running against an external force or torque, we show that the thermodynamic efficiency of such motors is universally bounded by an expression involving only experimentally accessible quantities. For motors pulling cargo through a viscous fluid, a universal bound for the corresponding Stokes efficiency follows as a variant. A similar result holds if mechanical force is used to synthesize molecules of high chemical potential. Crucially, no knowledge of the detailed underlying mechano-chemical mechanism is required for applying these bounds.

  3. 分子马达与布朗马达%MOLECULAR MOTORS AND BROWNIAN MOTORS

    Institute of Scientific and Technical Information of China (English)

    卓益忠; 赵同军; 展永

    2000-01-01

    综述了有关分子马达,主要是肌球蛋白马达和动 蛋白马达的实验研究进展情况,并对理论模型,特别是近年来广为流行的布朗马达模型作了 介绍和评论.最后展望了这一领域的发展前景及其所面临的挑战性问题.%Experimental studies on molecular motors,in parti cular myosin and kinesin motors are reviewed.Theoretical models,such as the Brow nian motor models are described and evaluated.Finally,the prospects and challen ges in this field are discussed.

  4. Advanced molecular devices based on light-driven molecular motors

    NARCIS (Netherlands)

    Chen, Jiawen

    2015-01-01

    Nature has provided a large collection of molecular machines and devices that are among the most amazing nanostructures on this planet. These machines are able to operate complex biological processes which are of great importance in our organisms. Inspired by these natural devices, artificial molecu

  5. Advanced molecular devices based on light-driven molecular motors

    NARCIS (Netherlands)

    Chen, Jiawen

    2015-01-01

    Nature has provided a large collection of molecular machines and devices that are among the most amazing nanostructures on this planet. These machines are able to operate complex biological processes which are of great importance in our organisms. Inspired by these natural devices, artificial

  6. Master Equation Approach to Molecular Motor's Directed Motion

    Institute of Scientific and Technical Information of China (English)

    FENG Juan; ZHUO Yi-Zhong

    2005-01-01

    @@ The master equation approach based on the periodic one-dimensional three-state hopping model is developed to study the molecular motor's directed motion. An explicit solution Px ( t ) is obtained for the probability distribution as a function of the time for any initial distribution Px(0) with all the transients included. We introduce dj to represent the sub-step lengths, which can reflect how the external load affects the individual rate via load distribution factors θ+j and θ-j. A wide variety of molecular motor behaviour under external load f can readily be obtained by the unequal-distance transition model with load-dependent transition rates. By comparison with the experiments, namely of the drift velocity v and the randomness parameter r versus adenosine triphosphate concentration and external load f, it is shown that the model presented here can rather satisfactorily explain the available data.

  7. Two-dimensional model of elastically coupled molecular motors

    Institute of Scientific and Technical Information of China (English)

    Zhang Hong-Wei; Wen Shu-Tang; Chen Gai-Rong; Li Yu-Xiao; Cao Zhong-Xing; Li Wei

    2012-01-01

    A flashing ratchet model of a two-headed molecular motor in a two-dimensional potential is proposed to simulate the hand-over-hand motion of kinesins.Extensive Langevin simulations of the model are performed.We discuss the dependences of motion and efficiency on the model parameters,including the external force and the temperature.A good qualitative agreement with the expected behavior is observed.

  8. Chemically optimizing operational efficiency of molecular rotary motors.

    Science.gov (United States)

    Conyard, Jamie; Cnossen, Arjen; Browne, Wesley R; Feringa, Ben L; Meech, Stephen R

    2014-07-09

    Unidirectional molecular rotary motors that harness photoinduced cis-trans (E-Z) isomerization are promising tools for the conversion of light energy to mechanical motion in nanoscale molecular machines. Considerable progress has been made in optimizing the frequency of ground-state rotation, but less attention has been focused on excited-state processes. Here the excited-state dynamics of a molecular motor with electron donor and acceptor substituents located to modify the excited-state reaction coordinate, without altering its stereochemistry, are studied. The substituents are shown to modify the photochemical yield of the isomerization without altering the motor frequency. By combining 50 fs resolution time-resolved fluorescence with ultrafast transient absorption spectroscopy the underlying excited-state dynamics are characterized. The Franck-Condon excited state relaxes in a few hundred femtoseconds to populate a lower energy dark state by a pathway that utilizes a volume conserving structural change. This is assigned to pyramidalization at a carbon atom of the isomerizing bridging double bond. The structure and energy of the dark state thus reached are a function of the substituent, with electron-withdrawing groups yielding a lower energy longer lived dark state. The dark state is coupled to the Franck-Condon state and decays on a picosecond time scale via a coordinate that is sensitive to solvent friction, such as rotation about the bridging bond. Neither subpicosecond nor picosecond dynamics are sensitive to solvent polarity, suggesting that intramolecular charge transfer and solvation are not key driving forces for the rate of the reaction. Instead steric factors and medium friction determine the reaction pathway, with the sterically remote substitution primarily influencing the energetics. Thus, these data indicate a chemical method of optimizing the efficiency of operation of these molecular motors without modifying their overall rotational frequency.

  9. Stokes Efficiency of Molecular Motor-Cargo Systems

    Science.gov (United States)

    2008-01-01

    2655, 1994. 11 F. Reif , Fundamentals of Statistical and Thermal Physics, McGraw-Hill, New York, NY, USA, 1985. 12 H. Kleinert, Path Integrals in...Quantum Mechanics , Statistics , Polymer Physics, and Financial Markets, World Scientific, River Edge, NJ, USA, 3rd edition, 2004. 13 A. Einstein...Efficiency of Molecular Motor-Cargo Systems Hongyun Wang1 and Hong Zhou2 1Department of Applied Mathematics and Statistics , University of California

  10. Periodic thermodynamics of laser-driven molecular motor

    Institute of Scientific and Technical Information of China (English)

    Li Dan; Zheng Wen-Wei; Wang Zhi-Song

    2008-01-01

    Operation of a laser-driven nano-motor inevitably generates a non-trivial amount of heat,which can possibly lead to instability or even hinder the motor's continual running.This work quantitatively examines the overheating problem for a recently proposed laser-operated molecular locomotive.We present a single-molecule cooling theory,in which molecular details of the locomotive system are explicitly treated.This theory is able to quantitatively predict cooling efficiency for various candidates of molecular systems for the locomotive,and also suggests concrete strategies for improving the locomotive's cooling.It is found that water environment is able to cool the hot locomotive down to room temperature within 100 picoseconds after photon absorption.This cooling time is a few orders of magnitude shorter than the typical time for laser operation,effectively preventing any overheating for the nano-locomotive.However,when the cooling is less effective in non-aqueous environment,residual heat may build up.A continuous running of the motor will then lead to a periodic thermodynamics,which is a common character of many laser-operated nano-devices.

  11. Mechanical transduction mechanisms of RecA-like molecular motors.

    Science.gov (United States)

    Liao, Jung-Chi

    2011-12-01

    A majority of ATP-dependent molecular motors are RecA-like proteins, performing diverse functions in biology. These RecA-like molecular motors consist of a highly conserved core containing the ATP-binding site. Here I examined how ATP binding within this core is coupled to the conformational changes of different RecA-like molecular motors. Conserved hydrogen bond networks and conformational changes revealed two major mechanical transduction mechanisms: (1) intra-domain conformational changes and (2) inter-domain conformational changes. The intra-domain mechanism has a significant hydrogen bond rearrangement within the domain containing the P-loop, causing relative motion between two parts of the protein. The inter-domain mechanism exhibits little conformational change in the P-loop domain. Instead, the major conformational change is observed between the P-loop domain and an adjacent domain or subunit containing the arginine finger. These differences in the mechanical transduction mechanisms may link to the underlying energy surface governing a Brownian ratchet or a power stroke.

  12. Ultrafast Excited State Dynamics in Molecular Motors: Coupling of Motor Length to Medium Viscosity.

    Science.gov (United States)

    Conyard, Jamie; Stacko, Peter; Chen, Jiawen; McDonagh, Sophie; Hall, Christopher R; Laptenok, Sergey P; Browne, Wesley R; Feringa, Ben L; Meech, Stephen R

    2017-03-07

    Photochemically driven molecular motors convert the energy of incident radiation to intramolecular rotational motion. The motor molecules considered here execute four step unidirectional rotational motion. This comprises a pair of successive light induced isomerizations to a metastable state followed by thermal helix inversions. The internal rotation of a large molecular unit required in these steps is expected to be sensitive to both the viscosity of the medium and the volume of the rotating unit. In this work, we describe a study of motor motion in both ground and excited states as a function of the size of the rotating units. The excited state decay is ultrafast, highly non-single exponential, and is best described by a sum of three exponential relaxation components. The average excited state decay time observed for a series of motors with substituents of increasing volume was determined. While substitution does affect the lifetime, the size of the substituent has only a minor effect. The solvent polarity dependence is also slight, but there is a significant solvent viscosity effect. Increasing the viscosity has no effect on the fastest of the three decay components, but it does lengthen the two slower decay times, consistent with them being associated with motion along an intramolecular coordinate displacing a large solvent volume. However, these slower relaxation times are again not a function of the size of the substituent. We conclude that excited state decay arises from motion along a coordinate which does not necessarily require complete rotation of the substituents through the solvent, but is instead more localized in the core structure of the motor. The decay of the metastable state to the ground state through a helix inversion occurs 14 orders of magnitude more slowly than the excited state decay, and was measured as a function of substituent size, solvent viscosity and temperature. In this case neither substituent size nor solvent viscosity influences

  13. Microtubules and associated molecular motors in Neurospora crassa.

    Science.gov (United States)

    Mouriño-Pérez, Rosa Reyna; Riquelme, Meritxell; Callejas-Negrete, Olga Alicia; Galván-Mendoza, José Iván

    2016-01-01

    The cytoskeleton provides structure, shape and movement to various cells. Microtubules (MTs) are tubular structures made of α and β-tubulin heterodimers organized in 13 protofilaments, forming a hollow cylinder. A vast group of MT-associated proteins determines the function, behavior and interaction of the MTs with other cellular components. Among these proteins, molecular motors such as the dynein-dynactin complex and kinesin superfamily play roles in MT organization and organelle transport. This article focuses on the MT cytoskeleton and associated molecular motors in the filamentous fungus Neurospora crassa In addition to reviewing current available information for this fungus and contrasting it with knowledge of other fungal species, we present new experimental results that support the role of dynein, dynactin and conventional kinesin in MT organization, dynamics and transport of subcellular structures (nuclei and secretory vesicles). In wild type hyphae of N. crassa, cytoplasmic MTs are arranged longitudinally along hyphae and display a helical curvature. They interlace with one another to form a network throughout the cytoplasm. N. crassa dynein and dynactin mutants have a scant and disorganized MT cytoskeleton, an erratic and reduced Spitzenkörper (Spk) and distorted hyphal morphology. In contrast, hyphae of mutants with defective conventional kinesin exhibit only minor disruptions in MT and Spk organization. Although nuclear positioning is affected in all mutants, the MT-associated motor proteins are not major contributors to nuclear movement during hyphal growth. Cytoplasmic bulk flow is the vehicle for nuclear displacement in growing hyphal regions of N. crassa Motors are involved in nuclei saltatory movements in both retrograde or anterograde direction. In the dynein and kinesin mutants, micro and macrovesicles can reach the Spk, although growth is slightly impaired and the Spk displays an erratic path. Hyphal growth requires MTs, and their associated

  14. Stochastic mechano-chemical kinetics of molecular motors: a multidisciplinary enterprise from a physicist's perspective

    CERN Document Server

    Chowdhury, Debashish

    2013-01-01

    A molecular motor is made of either a single macromolecule or a macromolecular complex. Just like their macroscopic counterparts, molecular motors "transduce" input energy into mechanical work. All the nano-motors considered here operate under isothermal conditions far from equilibrium. Moreover, one of the possible mechanisms of energy transduction, called Brownian ratchet, does not even have any macroscopic counterpart. But, molecular motor is not synonymous with Brownian ratchet; a large number of molecular motors execute a noisy power stroke, rather than operating as Brownian ratchet. We review not only the structural design and stochastic kinetics of individual single motors, but also their coordination, cooperation and competition as well as the assembly of multi-module motors in various intracellular kinetic processes. Although all the motors considered here execute mechanical movements, efficiency and power output are not necessarily good measures of performance of some motors. Among the intracellular...

  15. Traffic jams and shocks of molecular motors inside cellular protrusions.

    Science.gov (United States)

    Pinkoviezky, I; Gov, N S

    2014-05-01

    Molecular motors are involved in key transport processes inside actin-based cellular protrusions. The motors carry cargo proteins to the protrusion tip which participate in regulating the actin polymerization and play a key role in facilitating the growth and formation of such protrusions. It is observed that the motors accumulate at the tips of cellular protrusions and form aggregates that are found to drift towards the protrusion base at the rate of actin treadmilling. We present a one-dimensional driven lattice model, where motors become inactive after delivering their cargo at the tip, or by loosing their cargo to a cargoless neighbor. The results suggest that the experimental observations may be explained by the formation of traffic jams that form at the tip. The model is solved using a novel application of mean-field and shock analysis. We find a new class of shocks that undergo intermittent collapses. Extensions with attachment and detachment events and relevance to experiments are briefly described.

  16. Traffic Jams and Shocks of Molecular Motors inside Cellular Protrusions

    CERN Document Server

    Pinkoviezky, Itai

    2013-01-01

    Molecular motors are involved in key transport processes inside actin-based cellular protrusions. The motors carry cargo proteins to the protrusion tip which participate in regulating the actin polymerization, and play a key role in facilitating the growth and formation of such protrusions. It is observed that the motors accumulate at the tips of cellular protrusions, and in addition form aggregates that are found to drift towards the protrusion base at the rate of actin treadmilling. We present a one-dimensional driven lattice model, where motors become inactive after delivering their cargo at the tip, or by loosing their cargo to a cargo-less neighbor. The results suggest that the experimental observations may be explained by the formation of traffic jams that form at the tip. The model is solved using a novel application of mean-field and shock analysis. We find a new class of shocks that undergo intermittent collapses, and on average do not obey the Rankine-Hugoniot relation.

  17. Facile assembly of light-driven molecular motors onto a solid surface.

    Science.gov (United States)

    Chen, Jiawen; Chen, Kuang-Yen; Carroll, Gregory T; Feringa, Ben L

    2014-10-28

    In order to improve the rotary motion of surface assembled light-driven molecular motors, tetra-acid-functionalized motors were bound to an amine-coated quartz surface without prior activation of the acid groups. In contrast to earlier bipodal motors, the tetravalent motor showed no significant reduction in the rotation speed when attached to a surface.

  18. Facile assembly of light-driven molecular motors onto a solid surface

    NARCIS (Netherlands)

    Chen, Jiawen; Chen, Kuang-Yen; Carroll, Gregory T; Feringa, Ben L

    2014-01-01

    In order to improve the rotary motion of surface assembled light-driven molecular motors, tetra-acid-functionalized motors were bound to an amine-coated quartz surface without prior activation of the acid groups. In contrast to earlier bipodal motors, the tetravalent motor showed no significant redu

  19. Statistical determination of the step size of molecular motors

    Energy Technology Data Exchange (ETDEWEB)

    Neuman, K C; Saleh, O A; Lionnet, T; Lia, G; Allemand, J-F; Bensimon, D; Croquette, V [Laboratoire de Physique Statistique, Ecole Normale Superieure, 24 rue Lhomond, Paris 75005 (France)

    2005-11-30

    Molecular motors are enzymatic proteins that couple the consumption of chemical energy to mechanical displacement. In order to elucidate the translocation mechanisms of these enzymes, it is of fundamental importance to measure the physical step size. The step size can, in certain instances, be directly measured with single-molecule techniques; however, in the majority of cases individual steps are masked by noise. The step size can nevertheless be obtained from noisy single-molecule records through statistical methods. This analysis is analogous to determining the charge of the electron from current shot noise. We review methods for obtaining the step size based on analysing, in both the time and frequency domains, the variance in position from noisy single-molecule records of motor displacement. Additionally, we demonstrate how similar methods may be applied to measure the step size in bulk kinetic experiments.

  20. The role of molecular motor HKLP2 in spindle assembly

    OpenAIRE

    Vanneste, David

    2010-01-01

    Durante la división celular, tiene lugar el ensamblaje de la maquinaria macromolecular encargada de segregar los dos conjuntos de cromosomas en las dos células hijas. Esta maquinaria, el huso mitótico, es una matriz bipolar compuesta de microtúbulos y de proteínas que controlan la dinámica y la organización. Las quinesinas son motores moleculares que pueden ejercer fuerzas sobre los microtúbulos y organizarlos en el espacio para dar lugar al huso bipolar. Este estudio aporta evidencias del...

  1. Actin-based motility propelled by molecular motors

    Science.gov (United States)

    Upadyayula, Sai Pramod; Rangarajan, Murali

    2012-09-01

    Actin-based motility of Listeria monocytogenes propelled by filament end-tracking molecular motors has been simulated. Such systems may act as potential nanoscale actuators and shuttles useful in sorting and sensing biomolecules. Filaments are modeled as three-dimensional elastic springs distributed on one end of the capsule and persistently attached to the motile bacterial surface through an end-tracking motor complex. Filament distribution is random, and monomer concentration decreases linearly as a function of position on the bacterial surface. Filament growth rate increases with monomer concentration but decreases with the extent of compression. The growing filaments exert push-pull forces on the bacterial surface. In addition to forces, torques arise due to two factors—distribution of motors on the bacterial surface, and coupling of torsion upon growth due to the right-handed helicity of F-actin—causing the motile object to undergo simultaneous translation and rotation. The trajectory of the bacterium is simulated by performing a force and torque balance on the bacterium. All simulations use a fixed value of torsion. Simulations show strong alignment of the filaments and the long axis of the bacterium along the direction of motion. In the absence of torsion, the bacterial surface essentially moves along the direction of the long axis. When a small amount of the torsion is applied to the bacterial surface, the bacterium is seen to move in right-handed helical trajectories, consistent with experimental observations.

  2. Mesoscopic non-equilibrium thermodynamic analysis of molecular motors.

    Science.gov (United States)

    Kjelstrup, S; Rubi, J M; Pagonabarraga, I; Bedeaux, D

    2013-11-28

    We show that the kinetics of a molecular motor fueled by ATP and operating between a deactivated and an activated state can be derived from the principles of non-equilibrium thermodynamics applied to the mesoscopic domain. The activation by ATP, the possible slip of the motor, as well as the forward stepping carrying a load are viewed as slow diffusion along a reaction coordinate. Local equilibrium is assumed in the reaction coordinate spaces, making it possible to derive the non-equilibrium thermodynamic description. Using this scheme, we find expressions for the velocity of the motor, in terms of the driving force along the spacial coordinate, and for the chemical reaction that brings about activation, in terms of the chemical potentials of the reactants and products which maintain the cycle. The second law efficiency is defined, and the velocity corresponding to maximum power is obtained for myosin movement on actin. Experimental results fitting with the description are reviewed, giving a maximum efficiency of 0.45 at a myosin headgroup velocity of 5 × 10(-7) m s(-1). The formalism allows the introduction and test of meso-level models, which may be needed to explain experiments.

  3. Coexistence and efficiency of normal and anomalous transport by molecular motors in living cells

    CERN Document Server

    Goychuk, Igor; Metzler, R

    2013-01-01

    Recent experiments reveal both passive subdiffusion of various nanoparticles and anomalous active transport of such particles by molecular motors in the molecularly crowded environment of living biological cells. Passive and active microrheology reveals that the origin of this anomalous dynamics is due to the viscoelasticity of the intracellular fluid. How do molecular motors perform in such a highly viscous, dissipative environment? Can we explain the observed co-existence of the anomalous transport of relatively large particles of 100 to 500 nm in size by kinesin motors with the normal transport of smaller particles by the same molecular motors? What is the efficiency of molecular motors in the anomalous transport regime? Here we answer these seemingly conflicting questions and consistently explain experimental findings in a generalization of the well-known continuous diffusion model for molecular motors with two conformational states in which viscoelastic effects are included.

  4. Active fluidization of polymer networks through molecular motors.

    Science.gov (United States)

    Humphrey, D; Duggan, C; Saha, D; Smith, D; Käs, J

    2002-03-28

    Entangled polymer solutions and melts exhibit elastic, solid-like resistance to quick deformations and a viscous, fluid-like response to slow deformations. This viscoelastic behaviour reflects the dynamics of individual polymer chains driven by brownian motion: since individual chains can only move in a snake-like fashion through the mesh of surrounding polymer molecules, their diffusive transport, described by reptation, is so slow that the relaxation of suddenly imposed stress is delayed. Entangled polymer solutions and melts therefore elastically resist deforming motions that occur faster than the stress relaxation time. Here we show that the protein myosin II permits active control over the viscoelastic behaviour of actin filament solutions. We find that when each actin filament in a polymerized actin solution interacts with at least one myosin minifilament, the stress relaxation time of the polymer solution is significantly shortened. We attribute this effect to myosin's action as a 'molecular motor', which allows it to interact with randomly oriented actin filaments and push them through the solution, thus enhancing longitudinal filament motion. By superseding reptation with sliding motion, the molecular motors thus overcome a fundamental principle of complex fluids: that only depolymerization makes an entangled, isotropic polymer solution fluid for quick deformations.

  5. Stochastic thermodynamics of single enzymes and molecular motors.

    Science.gov (United States)

    Seifert, U

    2011-03-01

    For a single enzyme or molecular motor operating in an aqueous solution of non-equilibrated solute concentrations, a thermodynamic description is developed on the level of an individual trajectory of transitions between states. The concept of internal energy, intrinsic entropy and free energy for states follows from a microscopic description using one assumption on time scale separation. A first-law energy balance then allows the unique identification of the heat dissipated in one transition. Consistency with the second law on the ensemble level enforces both stochastic entropy as third contribution to the entropy change involved in one transition and the local detailed balance condition for the ratio between forward and backward rates for any transition. These results follow without assuming weak coupling between the enzyme and the solutes, ideal solution behavior or mass action law kinetics. The present approach highlights both the crucial role of the intrinsic entropy of each state and the physically questionable role of chemiostats for deriving the first law for molecular motors subject to an external force under realistic conditions.

  6. Influence of Random Potentials on the Current of the Molecular Motor Model

    Institute of Scientific and Technical Information of China (English)

    贾亚; 李家荣

    2001-01-01

    The current of the molecular motor model disturbed by random potentials, which involve the dichotomous and Ornstein-Uhlenbeck potentials, is studied using a finite-space correlation function. It is found that: (i) the amplitude and the correlation length of random potentials play opposing roles in the transport of the molecular motor model; (ii) a random potential with small amplitude and large correlation length is very useful in the molecular motor system.

  7. Traffic phenomena in biology: from molecular motors to organisms

    CERN Document Server

    Chowdhury, D; Nishinari, K; Chowdhury, Debashish; Schadschneider, Andreas; Nishinari, Katsuhiro

    2007-01-01

    Traffic-like collective movements are observed at almost all levels of biological systems. Molecular motor proteins like, for example, kinesin and dynein, which are the vehicles of almost all intra-cellular transport in eukayotic cells, sometimes encounter traffic jam that manifests as a disease of the organism. Similarly, traffic jam of collagenase MMP-1, which moves on the collagen fibrils of the extracellular matrix of vertebrates, has also been observed in recent experiments. Traffic-like movements of social insects like ants and termites on trails are, perhaps, more familiar in our everyday life. Experimental, theoretical and computational investigations in the last few years have led to a deeper understanding of the generic or common physical principles involved in these phenomena. In particular, some of the methods of non-equilibrium statistical mechanics, pioneered almost a hundred years ago by Einstein, Langevin and others, turned out to be powerful theoretical tools for quantitative analysis of mode...

  8. Control of Surface Wettability Using Tripodal Light-Activated Molecular Motors

    NARCIS (Netherlands)

    Chen, Kuang-Yen; Ivashenko, Oleksii; Carroll, Gregory T.; Robertus, Jort; Kistemaker, Jos C. M.; London, Gabor; Browne, Wesley R.; Rudolf, Petra; Feringa, Ben L.

    2014-01-01

    Monolayers of fluorinated light-driven molecular motors were synthesized and immobilized on gold films in an altitudinal orientation via tripodal stators. In this design the fimctionalized molecular motors are not interfering and preserve their rotary function on gold. The wettability of the

  9. Reprogrammable Assembly of Molecular Motor on Solid Surfaces via Dynamic Bonds.

    Science.gov (United States)

    Yu, Li; Sun, Jian; Wang, Qian; Guan, Yan; Zhou, Le; Zhang, Jingxuan; Zhang, Lanying; Yang, Huai

    2017-06-01

    Controllable assembly of molecular motors on solid surfaces is a fundamental issue for providing them to perform physical tasks. However, it can hardly be achieved by most previous methods due to their inherent limitations. Here, a general strategy is designed for the reprogrammable assembly of molecular motors on solid surfaces based on dynamic bonds. In this method, molecular motors with disulfide bonds can be remotely, reversibly, and precisely attached to solid surfaces with disulfide bonds, regardless of their chemical composition and microstructure. More importantly, it not only allows encoding geometric information referring to a pattern of molecular motors, but also enables erasing and re-encoding of geometric information via hemolytic photocleavage and recombination of disulfide bonds. Thus, solid surfaces can be regarded as "computer hardware", where molecular motors can be reformatted and reprogramed as geometric information. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. External forces influence the elastic coupling effects during cargo transport by molecular motors.

    Science.gov (United States)

    Berger, Florian; Keller, Corina; Klumpp, Stefan; Lipowsky, Reinhard

    2015-02-01

    Cellular transport is achieved by the cooperative action of molecular motors which are elastically linked to a common cargo. When the motors pull on the cargo at the same time, they experience fluctuating elastic strain forces induced by the stepping of the other motors. These elastic coupling forces can influence the motors' stepping and unbinding behavior and thereby the ability to transport cargos. Based on a generic single motor description, we introduce a framework that explains the response of two identical molecular motors to a constant external force. In particular, we relate the single motor parameters, the coupling strength and the external load force to the dynamics of the motor pair. We derive four distinct transport regimes and determine how the crossover lines between the regimes depend on the load force. Our description of the overall cargo dynamics takes into account relaxational displacements of the cargo caused by the unbinding of one motor. For large forces and weak elastic coupling these back-shifts dominate the displacements. To develop an intuitive understanding about motor cooperativity during cargo transport, we introduce a time scale for load sharing. This time scale allows us to predict how the regulation of single motor parameters influences the cooperativity. As an example, we show that up-regulating the single motor processivity enhances load sharing of the motor pair.

  11. Reactions of a fluorescent ATP analog, 2'-(5-dimethyl-aminonaphthalene-1-sulfonyl) amino-2'-deoxyATP, with E. coli F1-ATPase and its subunits: the roles of the high affinity binding site in the alpha subunit and the low affinity binding site in the beta subunit.

    Science.gov (United States)

    Matsuoka, I; Takeda, K; Futai, M; Tonomura, Y

    1982-11-01

    We performed kinetic studies on the reactions of a fluorescent ATP analog, 2'-(5-dimethyl-aminonaphthalene-1-sulfonyl) amino-2'-deoxyATP (DNS-ATP), with E. coli F1-ATPase (EF1) and its subunits, to clarify the role of each subunit in the ATPase reaction. The following results were obtained. 1. One mol of EF1, which contains nonexchangeable 2 mol ATP and 0.5 mol ADP, binds 3 mol of DNS-ATP. The apparent dissociation constant, in the presence of Mg2+, was 0.23 microM. Upon binding, the fluorescence intensity of DNS-ATP at 520 nm increased exponentially with t1/2 of 35 s, and reached 3.5 times the original fluorescence level. Following the fluorescence increase, DNS-ATP was hydrolyzed, and the fluorescence intensity maintained its enhanced level. 2. The addition of an excess of ATP over the EF1-DNS-nucleotide complex, in the presence of Mg2+, decreased the fluorescence intensity rapidly, indicating the acceleration of DNS-nucleotide release from EF1. ADP and GTP also decreased the fluorescence intensity. 3. DCCD markedly inhibited the accelerating effect of ATP on DNS-nucleotide release from EF1 and the EF1-DNS-ATPase or -ATPase activity in a steady state. On the other hand, DCCD only slightly inhibited the fluorescence increase of DNS-ATP, due to its binding to EF1, and the rate of single cleavage of 1 mol of DNS-ATP per mol of alpha subunit of EF1. 4. In the presence of Mg2+, 0.65-0.82 mol of DNS-ATP binds to 1 mol of the isolated alpha subunit of EF1 with an apparent dissociation constant of 0.06-0.07 microM. Upon binding, the fluorescence intensity of DNS-ATP at 520 nm increased 1.55 fold very rapidly (t1/2 less than 1 s). No hydrolysis of DNS-ATP was observed upon the addition of the isolated alpha subunit. The fluorescence intensity of DNS-ATP was unaffected by the addition of the isolated beta subunit. DNS-ATP was also unhydrolyzed by the isolated beta subunit. 5. EF1-ATPase was reconstituted from alpha, beta, and gamma subunits in the presence of Mg2+ and ATP

  12. Collective effects in intra-cellular molecular motor transport: coordination, cooperation and competetion

    CERN Document Server

    Chowdhury, D

    2006-01-01

    Molecular motors do not work in isolation {\\it in-vivo}. We highlight some of the coordinations, cooperations and competitions that determine the collective properties of molecular motors in eukaryotic cells. In the context of traffic-like movement of motors on a track, we emphasize the importance of single-motor bio-chemical cycle and enzymatic activity on their collective spatio-temporal organisation. Our modelling strategy is based on a synthesis- the same model describes the single-motor mechano-chemistry at sufficiently low densities whereas at higher densities it accounts for the collective flow properties and the density profiles of the motors. We consider two specific examples, namely, traffic of single-headed kinesin motors KIF1A on a microtubule track and ribosome traffic on a messenger RNA track.

  13. The reciprocal coordination and mechanics of molecular motors in living cells.

    Science.gov (United States)

    Laib, Jeneva A; Marin, John A; Bloodgood, Robert A; Guilford, William H

    2009-03-03

    Molecular motors in living cells are involved in whole-cell locomotion, contractility, developmental shape changes, and organelle movement and positioning. Whether motors of different directionality are functionally coordinated in cells or operate in a semirandom "tug of war" is unclear. We show here that anterograde and retrograde microtubule-based motors in the flagella of Chlamydomonas are regulated such that only motors of a common directionality are engaged at any single time. A laser trap was used to position microspheres on the plasma membrane of immobilized paralyzed Chlamydomonas flagella. The anterograde and retrograde movements of the microsphere were measured with nanometer resolution as microtubule-based motors engaged the transmembrane protein FMG-1. An average of 10 motors acted to move the microsphere in either direction. Reversal of direction during a transport event was uncommon, and quiescent periods separated every transport event, suggesting the coordinated and exclusive action of only a single motor type. After a jump to 32 degrees C, temperature-sensitive mutants of kinesin-2 (fla10) showed exclusively retrograde transport events, driven by 7 motors on average. These data suggest that molecular motors in living cells can be reciprocally coordinated to engage simultaneously in large numbers and for exclusive transport in a single direction, even when a mixed population of motors is present. This offers a unique model for studying the mechanics, regulation, and directional coordination of molecular motors in a living intracellular environment.

  14. Enantiopure Functional Molecular Motors Obtained by a Switchable Chiral-Resolution Process.

    Science.gov (United States)

    van Leeuwen, Thomas; Gan, Jefri; Kistemaker, Jos C M; Pizzolato, Stefano F; Chang, Mu-Chieh; Feringa, Ben L

    2016-05-17

    Molecular switches, rotors, and motors play an important role in the development of nano-machines and devices, as well as responsive and adaptive functional materials. For unidirectional rotors based on chiral overcrowded alkenes, their stereochemical homogeneity is of crucial importance. Herein, a method to obtain new and functionalizable overcrowded alkenes in enantiopure form is presented. The procedure involves a short synthesis of three steps and a solvent-switchable chiral resolution by using a readily available resolving agent. X-ray crystallography revealed the mode of binding of the motor with the resolving agent, as well as the absolute configuration of the motor. (1) H NMR and UV/Vis spectroscopy techniques were used to determine the dynamic behavior of this molecular motor. This method provides rapid access to ample amounts of enantiopure molecular motors, which will greatly facilitate the further development of responsive molecular systems based on chiral overcrowded alkenes.

  15. Fluctuation theorems for discrete kinetic models of molecular motors

    Science.gov (United States)

    Faggionato, Alessandra; Silvestri, Vittoria

    2017-04-01

    Motivated by discrete kinetic models for non-cooperative molecular motors on periodic tracks, we consider random walks (also not Markov) on quasi one dimensional (1d) lattices, obtained by gluing several copies of a fundamental graph in a linear fashion. We show that, for a suitable class of quasi-1d lattices, the large deviation rate function associated to the position of the walker satisfies a Gallavotti-Cohen symmetry for any choice of the dynamical parameters defining the stochastic walk. This class includes the linear model considered in Lacoste et al (2008 Phys. Rev. E 78 011915). We also derive fluctuation theorems for the time-integrated cycle currents and discuss how the matrix approach of Lacoste et al (2008 Phys. Rev. E 78 011915) can be extended to derive the above Gallavotti-Cohen symmetry for any Markov random walk on {Z} with periodic jump rates. Finally, we review in the present context some large deviation results of Faggionato and Silvestri (2017 Ann. Inst. Henri Poincaré 53 46-78) and give some specific examples with explicit computations.

  16. Molecular motors robustly drive active gels to a critically connected state

    CERN Document Server

    Alvarado, Jose; Sharma, Abhinav; MacKintosh, Fred C; Koenderink, Gijsje H

    2013-01-01

    Living systems often exhibit internal driving: active, molecular processes drive nonequilibrium phenomena such as metabolism or migration. Active gels constitute a fascinating class of internally driven matter, where molecular motors exert localized stresses inside polymer networks. There is evidence that network crosslinking is required to allow motors to induce macroscopic contraction. Yet a quantitative understanding of how network connectivity enables contraction is lacking. Here we show experimentally that myosin motors contract crosslinked actin polymer networks to clusters with a scale-free size distribution. This critical behavior occurs over an unexpectedly broad range of crosslink concentrations. To understand this robustness, we develop a quantitative model of contractile networks that takes into account network restructuring: motors reduce connectivity by forcing crosslinks to unbind. Paradoxically, to coordinate global contractions, motor activity should be low. Otherwise, motors drive initially ...

  17. Correlations and Symmetry of Interactions Influence Collective Dynamics of Molecular Motors

    CERN Document Server

    Celis-Garza, Daniel; Kolomeisky, Anatoly B

    2015-01-01

    Enzymatic molecules that actively support many cellular processes, including transport, cell division and cell motility, are known as motor proteins or molecular motors. Experimental studies indicate that they interact with each other and they frequently work together in large groups. To understand the mechanisms of collective behavior of motor proteins we study the effect of interactions in the transport of molecular motors along linear filaments. It is done by analyzing a recently introduced class of totally asymmetric exclusion processes that takes into account the intermolecular interactions via thermodynamically consistent approach. We develop a new theoretical method that allows us to compute analytically all dynamic properties of the system. Our analysis shows that correlations play important role in dynamics of interacting molecular motors. Surprisingly, we find that the correlations for repulsive interactions are weaker and more short-range than the correlations for the attractive interactions. In ad...

  18. 基于分子马达生物传感器技术的副溶血性弧菌分子分型方法的初步研究%A preliminary study on molecular typing method for Vibrio parahaemolyticus based on molecular motor biosensor

    Institute of Scientific and Technical Information of China (English)

    张捷; 李兆杰; 王煜; 张惠媛; 陆琳; 王静; 刘岩; 顾德周; 汪琦

    2013-01-01

    [Objective] To establish a simple and rapid molecular typing method tor Vibrio parahaemolyticus carrying and non-carrying virulence genes based on molecular motor.[Methods] Four probes specific to virulence genes tdh and trh,species-specific genes tlh and toxR of V.parahaemolyticus were synthesized,and four molecular motor biosensors were constructed by connecting probes to F0F1-ATPase molecular motors through biotin-streptavidin system,respectively.Ten strains of V.parahaemolyticus were classified by the biosensors,and the results were compared with PCR-Electrophoresis-Gel imaging results.Further more,the detection sensitivities and specificities of the molecular motor biosensors were studied.[Results] There were ten strains carrying tdh and none carrying trh,while all ten strains carry tlh and toxR,which was consisitent with the results of PCR-Electrophoresis-Gel imaging.The detection limits of molecular motor biosensors for tlh,toxR,tdh and trh were estimated to be 1 pg/reaction system,and the detection limits of PCR-Electrophoresis-Gel imaging for tlh,toxR,tdh and trh were estimated to be 10 pg/reaction system.The molecular motor biosensors could recognize tlh,toxR,tdh and trh of V.parahaemolyticus specifically.[Conclusion] A molecular typing method was constructed based on molecular motor biosensors and was used to diagnose the pathogenicity of V.parahaemolyticus rapidly and specifically.The detection limits was 10 times higher than those of PCR-Electrophoresis-Gel imaging.The method is easy,rapid,time-saving and labor-saving,especially suitable for the basic laboratories of CDC and port quarantine departments to perform suiveillance and epidemiological traceability of cholera.%[目的]建立基于分子马达技术的简便快速的分子分型方法,对携带和非携带毒力基因的副溶血性弧菌进行快速分类.[方法]以F0F1-ATPase为核心构建分子马达,以副溶血性弧菌毒力基因tdh、trh和种特异性

  19. Crossing the Border: Molecular Control of Motor Axon Exit

    Directory of Open Access Journals (Sweden)

    Arlene Bravo-Ambrosio

    2011-11-01

    Full Text Available Living organisms heavily rely on the function of motor circuits for their survival and for adapting to ever-changing environments. Unique among central nervous system (CNS neurons, motor neurons (MNs project their axons out of the CNS. Once in the periphery, motor axons navigate along highly stereotyped trajectories, often at considerable distances from their cell bodies, to innervate appropriate muscle targets. A key decision made by pathfinding motor axons is whether to exit the CNS through dorsal or ventral motor exit points (MEPs. In contrast to the major advances made in understanding the mechanisms that regulate the specification of MN subtypes and the innervation of limb muscles, remarkably little is known about how MN axons project out of the CNS. Nevertheless, a limited number of studies, mainly in Drosophila, have identified transcription factors, and in some cases candidate downstream effector molecules, that are required for motor axons to exit the spinal cord. Notably, specialized neural crest cell derivatives, referred to as Boundary Cap (BC cells, pre-figure and demarcate MEPs in vertebrates. Surprisingly, however, BC cells are not required for MN axon exit, but rather restrict MN cell bodies from ectopically migrating along their axons out of the CNS. Here, we describe the small set of studies that have addressed motor axon exit in Drosophila and vertebrates, and discuss our fragmentary knowledge of the mechanisms, which guide motor axons out of the CNS.

  20. How molecular motors are arranged on a cargo is important for vesicular transport.

    Science.gov (United States)

    Erickson, Robert P; Jia, Zhiyuan; Gross, Steven P; Yu, Clare C

    2011-05-01

    The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself--and motor organization on the cargo--affects transport has not been considered. To address this, we have developed a three-dimensional Monte Carlo simulation of motors transporting a spherical cargo, subject to thermal fluctuations that produce both rotational and translational diffusion. We found that these fluctuations could exert a load on the motor(s), significantly decreasing the mean travel distance and velocity of large cargos, especially at large viscosities. In addition, the presence of the cargo could dramatically help the motor to bind productively to the microtubule: the relatively slow translational and rotational diffusion of moderately sized cargos gave the motors ample opportunity to bind to a microtubule before the motor/cargo ensemble diffuses out of range of that microtubule. For rapidly diffusing cargos, the probability of their binding to a microtubule was high if there were nearby microtubules that they could easily reach by translational diffusion. Our simulations found that one reason why motors may be approximately 100 nm long is to improve their 'on' rates when attached to comparably sized cargos. Finally, our results suggested that to efficiently regulate the number of active motors, motors should be clustered together rather than spread randomly over the surface of the cargo. While our simulation uses the specific parameters for kinesin, these effects result from generic properties of the motors, cargos, and filaments, so they should apply to other motors as well.

  1. How molecular motors are arranged on a cargo is important for vesicular transport.

    Directory of Open Access Journals (Sweden)

    Robert P Erickson

    2011-05-01

    Full Text Available The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself--and motor organization on the cargo--affects transport has not been considered. To address this, we have developed a three-dimensional Monte Carlo simulation of motors transporting a spherical cargo, subject to thermal fluctuations that produce both rotational and translational diffusion. We found that these fluctuations could exert a load on the motor(s, significantly decreasing the mean travel distance and velocity of large cargos, especially at large viscosities. In addition, the presence of the cargo could dramatically help the motor to bind productively to the microtubule: the relatively slow translational and rotational diffusion of moderately sized cargos gave the motors ample opportunity to bind to a microtubule before the motor/cargo ensemble diffuses out of range of that microtubule. For rapidly diffusing cargos, the probability of their binding to a microtubule was high if there were nearby microtubules that they could easily reach by translational diffusion. Our simulations found that one reason why motors may be approximately 100 nm long is to improve their 'on' rates when attached to comparably sized cargos. Finally, our results suggested that to efficiently regulate the number of active motors, motors should be clustered together rather than spread randomly over the surface of the cargo. While our simulation uses the specific parameters for kinesin, these effects result from generic properties of the motors, cargos, and filaments, so they should apply to other motors as well.

  2. Can molecular motors drive distance measurements in injured neurons?

    Directory of Open Access Journals (Sweden)

    Naaman Kam

    2009-08-01

    Full Text Available Injury to nerve axons induces diverse responses in neuronal cell bodies, some of which are influenced by the distance from the site of injury. This suggests that neurons have the capacity to estimate the distance of the injury site from their cell body. Recent work has shown that the molecular motor dynein transports importin-mediated retrograde signaling complexes from axonal lesion sites to cell bodies, raising the question whether dynein-based mechanisms enable axonal distance estimations in injured neurons? We used computer simulations to examine mechanisms that may provide nerve cells with dynein-dependent distance assessment capabilities. A multiple-signals model was postulated based on the time delay between the arrival of two or more signals produced at the site of injury-a rapid signal carried by action potentials or similar mechanisms and slower signals carried by dynein. The time delay between the arrivals of these two types of signals should reflect the distance traversed, and simulations of this model show that it can indeed provide a basis for distance measurements in the context of nerve injuries. The analyses indicate that the suggested mechanism can allow nerve cells to discriminate between distances differing by 10% or more of their total axon length, and suggest that dynein-based retrograde signaling in neurons can be utilized for this purpose over different scales of nerves and organisms. Moreover, such a mechanism might also function in synapse to nucleus signaling in uninjured neurons. This could potentially allow a neuron to dynamically sense the relative lengths of its processes on an ongoing basis, enabling appropriate metabolic output from cell body to processes.

  3. Chiral Hydrogen Bond Environment Providing Unidirectional Rotation in Photoactive Molecular Motors.

    Science.gov (United States)

    García-Iriepa, Cristina; Marazzi, Marco; Zapata, Felipe; Valentini, Alessio; Sampedro, Diego; Frutos, Luis Manuel

    2013-05-02

    Generation of a chiral hydrogen bond environment in efficient molecular photoswitches is proposed as a novel strategy for the design of photoactive molecular motors. Here, the following strategy is used to design a retinal-based motor presenting singular properties: (i) a single excitation wavelength is needed to complete the unidirectional rotation process (360°); (ii) the absence of any thermal step permits the process to take place at low temperatures; and (iii) the ultrafast process permits high rotational frequencies.

  4. From the Cover: Cooperative extraction of membrane nanotubes by molecular motors

    Science.gov (United States)

    Leduc, Cécile; Campàs, Otger; Zeldovich, Konstantin B.; Roux, Aurélien; Jolimaitre, Pascale; Bourel-Bonnet, Line; Goud, Bruno; Joanny, Jean-François; Bassereau, Patricia; Prost, Jacques

    2004-12-01

    In eukaryotic cells, nanotubes represent a substantial fraction of transport intermediates between organelles. They are extracted from membranes by molecular motors walking along microtubules. We previously showed that kinesins fixed on giant unilamellar vesicles in contact with microtubules are sufficient to form nanotubes in vitro. Motors were attached to the membrane through beads, thus facilitating cooperative effects. Koster et al. [Koster, G., VanDuijn, M., Hofs, B. & Dogterom, M. (2003) Proc. Natl. Acad. Sci. USA 100, 15583-15588] proposed that motors could dynamically cluster at the tip of tubes when they are individually attached to the membrane. We demonstrate, in a recently designed experimental system, the existence of an accumulation of motors allowing tube extraction. We determine the motor density along a tube by using fluorescence intensity measurements. We also perform a theoretical analysis describing the dynamics of motors and tube growth. The only adjustable parameter is the motor binding rate onto microtubules, which we measure to be 4.7 ± 2.4 s-1. In addition, we quantitatively determine, for a given membrane tension, the existence of a threshold in motor density on the vesicle above which nanotubes can be formed. We find that the number of motors pulling a tube can range from four at threshold to a few tens away from it. The threshold in motor density (or in membrane tension at constant motor density) could be important for the understanding of membrane traffic regulation in cells. giant unilamellar vesicle | intracellular transport | kinesin | membrane tubule | traffic jam

  5. Transport dynamics of molecular motors that switch between an active and inactive state.

    Science.gov (United States)

    Pinkoviezky, I; Gov, N S

    2013-08-01

    Molecular motors are involved in key transport processes in the cell. Many of these motors can switch from an active to a nonactive state, either spontaneously or depending on their interaction with other molecules. When active, the motors move processively along the filaments, while when inactive they are stationary. We treat here the simple case of spontaneously switching motors, between the active and inactive states, along an open linear track. We use our recent analogy with vehicular traffic, where we go beyond the mean-field description. We map the phase diagram of this system, and find that it clearly breaks the symmetry between the different phases, as compared to the standard total asymmetric exclusion process. We make several predictions that may be testable using molecular motors in vitro and in living cells.

  6. Computational Design of a Family of Light-Driven Rotary Molecular Motors with Improved Quantum Efficiency.

    Science.gov (United States)

    Nikiforov, Alexander; Gamez, Jose A; Thiel, Walter; Filatov, Michael

    2016-01-07

    Two new light-driven molecular rotary motors based on the N-alkylated indanylidene benzopyrrole frameworks are proposed and studied using quantum chemical calculations and nonadiabatic molecular dynamics simulations. These new motors perform pure axial rotation, and the photochemical steps of the rotary cycle are dominated by the fast bond-length-alternation motion that enables ultrafast access to the S1/S0 intersection. The new motors are predicted to display a quantum efficiency higher than that of the currently available synthetic all-hydrocarbon motors. Remarkably, the quantum efficiency is not governed by the topography (peaked versus sloped) of the minimum-energy conical intersection, whereas the S1 decay time depends on the topography as well as on the energy of the intersection relative to the S1 minimum. It is the axial chirality (helicity), rather than the point chirality, that controls the sense of rotation of the motor.

  7. Towards dynamic control of wettability by using functionalized altitudinal molecular motors on solid surfaces.

    Science.gov (United States)

    London, Gábor; Chen, Kuang-Yen; Carroll, Gregory T; Feringa, Ben L

    2013-08-05

    We report the synthesis of altitudinal molecular motors that contain functional groups in their rotor part. In an approach to achieve dynamic control over the properties of solid surfaces, a hydrophobic perfluorobutyl chain and a relatively hydrophilic cyano group were introduced to the rotor part of the motors. Molecular motors were attached to quartz surfaces by using interfacial 1,3-dipolar cycloadditions. To test the effect of the functional groups on the rotary motion, photochemical and thermal isomerization studies of the motors were performed both in solution and when attached to the surface. We found that the substituents have no significant effect on the thermal and photochemical processes, and the functionalized motors preserved their rotary function both in solution and on a quartz surface. Preliminary results on the influence of the functional groups on surface wettability are also described.

  8. Exclusion and Hierarchy of Time Scales Lead to Spatial Segregation of Molecular Motors in Cellular Protrusions

    Science.gov (United States)

    Pinkoviezky, I.; Gov, N. S.

    2017-01-01

    Molecular motors that carry cargo along biopolymer filaments within cells play a crucial role in the functioning of the cell. In particular, these motors are essential for the formation and maintenance of the cellular protrusions that play key roles in motility and specific functionalities, such as the stereocilia in hair cells. Typically, there are several species of motors, carrying different cargos, that share the same track. Furthermore, it was observed that in the mature stereocilia, the different motors occupy well-segregated bands as a function of distance from the tip. We use a totally asymmetric exclusion process model with two- and three-motor species, to study the conditions that give rise to such spatial patterns. We find that the well-segregated bands appear for motors with a strong hierarchy of attachment or detachment rates. This is a striking example of pattern formation in nonequilibrium, low-dimensional systems.

  9. Mechanism of cooperative behaviour in systems of slow and fast molecular motors.

    Science.gov (United States)

    Larson, Adam G; Landahl, Eric C; Rice, Sarah E

    2009-06-28

    Two recent theoretical advances have described cargo transport by multiple identical motors and by multiple oppositely directed, but otherwise identical motors [M. J. Muller, S. Klumpp and R. Lipowsky, Proc. Natl. Acad. Sci. U. S. A., 2008, 105(12), 4609-4614; S. Klumpp and R. Lipowsky, Proc. Natl. Acad. Sci. U. S. A., 2005, 102(48), 17284-17289]. Here, we combine a similar theoretical approach with a simple experiment to describe the behaviour of a system comprised of slow and fast molecular motors having the same directionality. We observed the movement of microtubules by mixtures of slow and fast kinesin motors attached to a glass coverslip in a classic sliding filament assay. The motors are identical, except that the slow ones contain five point mutations that collectively reduce their velocity approximately 15-fold without compromising maximal ATPase activity. Our results indicate that a small fraction of fast motors are able to accelerate the dissociation of slow motors from microtubules. Because of this, a sharp, highly cooperative transition occurs from slow to fast microtubule movement as the relative number of fast motors in the assay is increased. Microtubules move at half-maximal velocity when only 15% of the motors in the assay are fast. Our model indicates that this behaviour depends primarily on the relative motor velocities and the asymmetry between their forward and backward dissociation forces. It weakly depends on the number of motors and their processivity. We predict that movement of cargoes bound to two types of motors having very different velocities will be dominated by one or the other motor. Therefore, cargoes can potentially undergo abrupt changes in movement in response to regulatory mechanisms acting on only a small fraction of motors.

  10. Kinetic mechanism of DNA translocation by the RSC molecular motor.

    Science.gov (United States)

    Eastlund, Allen; Malik, Shuja Shafi; Fischer, Christopher J

    2013-04-15

    ATP-dependent nucleosome repositioning by chromatin remodeling enzymes requires the translocation of these enzymes along the nucleosomal DNA. Using a fluorescence stopped-flow assay we monitored DNA translocation by a minimal RSC motor and through global analysis of these time courses we have determined that this motor has a macroscopic translocation rate of 2.9 bp/s with a step size of 1.24 bp. From the complementary quantitative analysis of the associated time courses of ATP consumption during DNA translocation we have determined that this motor has an efficiency of 3.0 ATP/bp, which is slightly less that the efficiency observed for several genetically related DNA helicases and which likely results from random pausing by the motor during translocation. Nevertheless, this motor is able to exert enough force during translocation to displace streptavidin from biotinylated DNA. Taken together these results are the necessary first step for quantifying both the role of DNA translocation in nucleosome repositioning by RSC and the efficiency at which RSC couples ATP binding and hydrolysis to nucleosome repositioning.

  11. Biophysics of filament length regulation by molecular motors

    CERN Document Server

    Kuan, Hui-Shun

    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 kines...

  12. Increased speed of rotation for the smallest light-driven molecular motor

    NARCIS (Netherlands)

    ter Wiel, MKJ; van Delden, RA; Meetsma, A; Feringa, BL; Delden, Richard A. van; Feringa, Bernard

    2003-01-01

    In this paper we present the smallest artificial light-driven molecular motor consisting of only 28 carbon and 24 hydrogen atoms. The concept of controlling directionality of rotary movement at the molecular level by introduction of a stereogenic center next to the central olefinic bond of a sterica

  13. Molecular motors: how to make models that can be used to convey the concept of molecular ratchets and thermal capture.

    Science.gov (United States)

    DoHarris, Lindsay; Giesler, Amanda; Humber, Brent; Sukumar, Aravin; Janssen, Luke J

    2011-06-01

    A wide variety of cellular processes use molecular motors, including processive motors that move along some form of track (e.g., myosin with actin, kinesin or dynein with tubulin) and polymerases that move along a template (e.g., DNA and RNA polymerases, ribosomes). In trying to understand how these molecular motors actually move, many apply their understanding of how man-made motors work: the latter use some form of energy to exert a force or torque on its load. However, quite a different mechanism has been proposed to possibly account for the movement of molecular motors. Rather than hydrolyzing ATP to push or pull their load, they might use their own thermal vibrational energy as well as that of their load and their environment to move the load, capturing those movements that occur along a desired vector or axis and resisting others; ATP hydrolysis is required to make backward movements impossible. This intriguing thermal capture or Brownian ratchet model is relatively more difficult to convey to students. In this report, we describe several teaching aids that are very easily constructed using widely available household materials to convey the concept of a molecular ratchet.

  14. Intrinsic irreversibility limits the efficiency of multidimensional molecular motors

    Science.gov (United States)

    Jack, M. W.; Tumlin, C.

    2016-05-01

    We consider the efficiency limits of Brownian motors able to extract work from the temperature difference between reservoirs or from external thermodynamic forces. These systems can operate in a variety of modes, including as isothermal engines, heat engines, refrigerators, and heat pumps. We derive analytical results showing that certain classes of multidimensional Brownian motor, including the Smoluchowski-Feynman ratchet, are unable to attain perfect efficiency (Carnot efficiency for heat engines). This demonstrates the presence of intrinsic irreversibilities in their operating mechanism. We present numerical simulations showing that in some cases the loss process that limits efficiency is associated with vortices in the probability current.

  15. Intrinsic irreversibility limits the efficiency of multidimensional molecular motors.

    Science.gov (United States)

    Jack, M W; Tumlin, C

    2016-05-01

    We consider the efficiency limits of Brownian motors able to extract work from the temperature difference between reservoirs or from external thermodynamic forces. These systems can operate in a variety of modes, including as isothermal engines, heat engines, refrigerators, and heat pumps. We derive analytical results showing that certain classes of multidimensional Brownian motor, including the Smoluchowski-Feynman ratchet, are unable to attain perfect efficiency (Carnot efficiency for heat engines). This demonstrates the presence of intrinsic irreversibilities in their operating mechanism. We present numerical simulations showing that in some cases the loss process that limits efficiency is associated with vortices in the probability current.

  16. Molecular motors pulling cargos in the viscoelastic cytosol: how power strokes beat subdiffusion.

    Science.gov (United States)

    Goychuk, Igor; Kharchenko, Vasyl O; Metzler, Ralf

    2014-08-21

    The discovery of anomalous diffusion of larger biopolymers and submicron tracers such as endogenous granules, organelles, or virus capsids in living cells, attributed to the viscoelastic nature of the cytoplasm, provokes the question whether this complex environment equally impacts the active intracellular transport of submicron cargos by molecular motors such as kinesins: does the passive anomalous diffusion of free cargo always imply its anomalously slow active transport by motors, the mean transport distance along microtubule growing sublinearly rather than linearly in time? Here we analyze this question within the widely used two-state Brownian ratchet model of kinesin motors based on the continuous-state diffusion along microtubules driven by a flashing binding potential, where the cargo particle is elastically attached to the motor. Depending on the cargo size, the loading force, the amplitude of the binding potential, the turnover frequency of the molecular motor enzyme, and the linker stiffness we demonstrate that the motor transport may turn out either normal or anomalous, as indeed measured experimentally. We show how a highly efficient normal active transport mediated by motors may emerge despite the passive anomalous diffusion of the cargo, and study the intricate effects of the elastic linker. Under different, well specified conditions the microtubule-based motor transport becomes anomalously slow and thus significantly less efficient.

  17. Tuning the Rotation Rate of Light-Driven Molecular Motors

    NARCIS (Netherlands)

    Bauer, Jurica; Hou, Lili; Kistemaker, Jos C. M.; Feringa, Bernard

    2014-01-01

    Overcrowded alkenes are among the most promising artificial mol. motors because of their ability to undergo repetitive light-driven unidirectional rotary motion around the central C=C bond. The exceptional features of these mols. render them highly useful for a no. of applications in nanotechnol. Ma

  18. How molecular motors work in the crowded environment of living cells: coexistence and efficiency of normal and anomalous transport.

    Science.gov (United States)

    Goychuk, Igor; Kharchenko, Vasyl O; Metzler, Ralf

    2014-01-01

    Recent experiments reveal both passive subdiffusion of various nanoparticles and anomalous active transport of such particles by molecular motors in the molecularly crowded environment of living biological cells. Passive and active microrheology reveals that the origin of this anomalous dynamics is due to the viscoelasticity of the intracellular fluid. How do molecular motors perform in such a highly viscous, dissipative environment? Can we explain the observed co-existence of the anomalous transport of relatively large particles of 100 to 500 nm in size by kinesin motors with the normal transport of smaller particles by the same molecular motors? What is the efficiency of molecular motors in the anomalous transport regime? Here we answer these seemingly conflicting questions and consistently explain experimental findings in a generalization of the well-known continuous diffusion model for molecular motors with two conformational states in which viscoelastic effects are included.

  19. How molecular motors work in the crowded environment of living cells: coexistence and efficiency of normal and anomalous transport.

    Directory of Open Access Journals (Sweden)

    Igor Goychuk

    Full Text Available Recent experiments reveal both passive subdiffusion of various nanoparticles and anomalous active transport of such particles by molecular motors in the molecularly crowded environment of living biological cells. Passive and active microrheology reveals that the origin of this anomalous dynamics is due to the viscoelasticity of the intracellular fluid. How do molecular motors perform in such a highly viscous, dissipative environment? Can we explain the observed co-existence of the anomalous transport of relatively large particles of 100 to 500 nm in size by kinesin motors with the normal transport of smaller particles by the same molecular motors? What is the efficiency of molecular motors in the anomalous transport regime? Here we answer these seemingly conflicting questions and consistently explain experimental findings in a generalization of the well-known continuous diffusion model for molecular motors with two conformational states in which viscoelastic effects are included.

  20. Increased speed of rotation for the smallest light-driven molecular motor.

    Science.gov (United States)

    ter Wiel, Matthijs K J; van Delden, Richard A; Meetsma, Auke; Feringa, Ben L

    2003-12-10

    In this paper we present the smallest artificial light-driven molecular motor consisting of only 28 carbon and 24 hydrogen atoms. The concept of controlling directionality of rotary movement at the molecular level by introduction of a stereogenic center next to the central olefinic bond of a sterically overcrowded alkene does not only hold for molecular motors with six-membered rings, but is also applicable to achieve the unidirectional movement for molecular motors having five-membered rings. Although X-ray analyses show that the five-membered rings in the cis- and trans-isomer of the new molecular motor are nearly flat, the energy differences between the (pseudo-)diaxial and (pseudo-)diequatorial conformations of the methyl substituents in both isomers are still large enough to direct the rotation of one-half of the molecule with respect to the other half in a clockwise fashion. The full rotary cycle comprises four consecutive steps: two photochemical isomerizations each followed by a thermal helix inversion. Both photochemical cis-trans isomerizations proceed with a preference for the unstable diequatorial isomers over the stable diaxial isomers. The thermal barriers for helix inversion of this motor molecule have decreased dramatically compared to its six-membered ring analogue, the half-life of the fastest step being only 18 s at room temperature.

  1. Tug-of-war between opposing molecular motors explains chromosomal oscillation during mitosis.

    Science.gov (United States)

    Sutradhar, S; Paul, R

    2014-03-07

    Chromosomes move towards and away from the centrosomes during the mitosis. This oscillation is observed when the kinetochore, a specific protein structure on the chromosome is captured by centrosome-nucleated polymer called microtubules. We present a computational model, incorporating activities of various molecular motors and microtubule dynamics, to demonstrate the observed oscillation. The model is robust and is not restricted to any particular cell type. Quantifying the average velocity, amplitude and periodicity of the chromosomal oscillation, we compare numerical results with the available experimental data. Our analysis supports a tug-of-war like mechanism between opposing motors that changes the course of chromosomal oscillation. It turns out that, various modes of oscillation can be fully understood by assembling the dynamics of molecular motors. Near the stall regime, when opposing motors are engaged in a tug-of-war, sufficiently large kinetochore-microtubule generated force may prolong the stall durations.

  2. Review on Modeling Molecular Motor%分子马达模型综述

    Institute of Scientific and Technical Information of China (English)

    王先菊; 艾保全; 刘良钢

    2001-01-01

    The structure and function of three kinds of motor proteins are introduced. The fundamental importance on studying molecular motor in living systems is also discribed. With detailed review on several archetype theoretical models, the progress and application on modeling molecule motor are presented.%介绍三类马达酶的结构,功能和生命体内分子马达的研究状况,并详细介绍几类典型分子马达的理论模型,同时展望了分子马达的发展前景和应用.

  3. Future challenges in single-molecule fluorescence and laser trap approaches to studies of molecular motors.

    Science.gov (United States)

    Elting, Mary Williard; Spudich, James A

    2012-12-11

    Single-molecule analysis is a powerful modern form of biochemistry, in which individual kinetic steps of a catalytic cycle of an enzyme can be explored in exquisite detail. Both single-molecule fluorescence and single-molecule force techniques have been widely used to characterize a number of protein systems. We focus here on molecular motors as a paradigm. We describe two areas where we expect to see exciting developments in the near future: first, characterizing the coupling of force production to chemical and mechanical changes in motors, and second, understanding how multiple motors work together in the environment of the cell.

  4. Molecular and Functional Characterization of the Developing Respiratory Motor Circuit

    OpenAIRE

    2015-01-01

    The faithful and sophisticated control of motor neurons (MNs) allows for our ability to walk, chew, breathe, and speak. This dissertation is focused on the characterization of MNs and the intricate circuitry that are involved in the control of these MNs that surround the airways. The relevance of this study goes beyond satisfying our curiosity of the physiology of breathing. This knowledge is critical in their application in respiratory medicine and speech rehabilitation – as the same set of ...

  5. Stepping and crowding of molecular motors: statistical kinetics from an exclusion process perspective.

    Science.gov (United States)

    Ciandrini, Luca; Romano, M Carmen; Parmeggiani, Andrea

    2014-09-02

    Motor enzymes are remarkable molecular machines that use the energy derived from the hydrolysis of a nucleoside triphosphate to generate mechanical movement, achieved through different steps that constitute their kinetic cycle. These macromolecules, nowadays investigated with advanced experimental techniques to unveil their molecular mechanisms and the properties of their kinetic cycles, are implicated in many biological processes, ranging from biopolymerization (e.g., RNA polymerases and ribosomes) to intracellular transport (motor proteins such as kinesins or dyneins). Although the kinetics of individual motors is well studied on both theoretical and experimental grounds, the repercussions of their stepping cycle on the collective dynamics still remains unclear. Advances in this direction will improve our comprehension of transport process in the natural intracellular medium, where processive motor enzymes might operate in crowded conditions. In this work, we therefore extend contemporary statistical kinetic analysis to study collective transport phenomena of motors in terms of lattice gas models belonging to the exclusion process class. Via numerical simulations, we show how to interpret and use the randomness calculated from single particle trajectories in crowded conditions. Importantly, we also show that time fluctuations and non-Poissonian behavior are intrinsically related to spatial correlations and the emergence of large, but finite, clusters of comoving motors. The properties unveiled by our analysis have important biological implications on the collective transport characteristics of processive motor enzymes in crowded conditions.

  6. Muscle activation described with a differential equation model for large ensembles of locally coupled molecular motors.

    Science.gov (United States)

    Walcott, Sam

    2014-10-01

    Molecular motors, by turning chemical energy into mechanical work, are responsible for active cellular processes. Often groups of these motors work together to perform their biological role. Motors in an ensemble are coupled and exhibit complex emergent behavior. Although large motor ensembles can be modeled with partial differential equations (PDEs) by assuming that molecules function independently of their neighbors, this assumption is violated when motors are coupled locally. It is therefore unclear how to describe the ensemble behavior of the locally coupled motors responsible for biological processes such as calcium-dependent skeletal muscle activation. Here we develop a theory to describe locally coupled motor ensembles and apply the theory to skeletal muscle activation. The central idea is that a muscle filament can be divided into two phases: an active and an inactive phase. Dynamic changes in the relative size of these phases are described by a set of linear ordinary differential equations (ODEs). As the dynamics of the active phase are described by PDEs, muscle activation is governed by a set of coupled ODEs and PDEs, building on previous PDE models. With comparison to Monte Carlo simulations, we demonstrate that the theory captures the behavior of locally coupled ensembles. The theory also plausibly describes and predicts muscle experiments from molecular to whole muscle scales, suggesting that a micro- to macroscale muscle model is within reach.

  7. Self-organization of waves and pulse trains by molecular motors in cellular protrusions.

    Science.gov (United States)

    Yochelis, A; Ebrahim, S; Millis, B; Cui, R; Kachar, B; Naoz, M; Gov, N S

    2015-09-03

    Actin-based cellular protrusions are an ubiquitous feature of cells, performing a variety of critical functions ranging from cell-cell communication to cell motility. The formation and maintenance of these protrusions relies on the transport of proteins via myosin motors, to the protrusion tip. While tip-directed motion leads to accumulation of motors (and their molecular cargo) at the protrusion tip, it is observed that motors also form rearward moving, periodic and isolated aggregates. The origins and mechanisms of these aggregates, and whether they are important for the recycling of motors, remain open puzzles. Motivated by novel myosin-XV experiments, a mass conserving reaction-diffusion-advection model is proposed. The model incorporates a non-linear cooperative interaction between motors, which converts them between an active and an inactive state. Specifically, the type of aggregate formed (traveling waves or pulse-trains) is linked to the kinetics of motors at the protrusion tip which is introduced by a boundary condition. These pattern selection mechanisms are found not only to qualitatively agree with empirical observations but open new vistas to the transport phenomena by molecular motors in general.

  8. Influence of molecular motors on the motion of particles in viscoelastic media.

    Science.gov (United States)

    Bouzat, Sebastián

    2014-06-01

    We study theoretically and by numerical simulations the motion of particles driven by molecular motors in a viscoelastic medium representing the cell cytoplasm. For this, we consider a generalized Langevin equation coupled to a stochastic stepping dynamics for the motors that takes into account the action of each motor separately. In the absence of motors, the model produces subdiffusive motion of particles characterized by a power-law scaling of the mean square displacement versus the lag time as t^{α}, with 0motors can induce a transition to a superdiffusive regime at large lag times with the characteristics of those found in experiments reported in the literature. We also show that at small lag times, the motors can act as static crosslinkers that slow down the natural subdiffusive transport. An analysis of previously reported experimental data in the relevant time scales provides evidence of this phenomenon. Finally, we study the effect of a harmonic potential representing an optical trap, and we show a way to approach to a macroscopic description of the active transport in cells. This last point stresses the relevance of the molecular motors for generating not only directed motion to specific targets, but also fast diffusivelike random motion.

  9. A Molecular Motor, KIF13A, Controls Anxiety by Transporting the Serotonin Type 1A Receptor

    Directory of Open Access Journals (Sweden)

    Ruyun Zhou

    2013-02-01

    Full Text Available Molecular motors are fundamental to neuronal morphogenesis and function. However, the extent to which molecular motors are involved in higher brain functions remains largely unknown. In this study, we show that mice deficient in the kinesin family motor protein KIF13A (Kif13a−/− mice exhibit elevated anxiety-related behavioral phenotypes, probably because of a reduction in 5HT1A receptor (5HT1AR transport. The cell-surface expression level of the 5HT1AR was reduced in KIF13A-knockdown neuroblastoma cells and Kif13a−/− hippocampal neurons. Biochemical analysis showed that the forkhead-associated (FHA domain of KIF13A and an intracellular loop of the 5HT1AR are the interface between the motor and cargo vesicles. A minimotor consisting of the motor and FHA domains is able to transport 5HT1AR-carrying organelles in in vitro reconstitution assays. Collectively, our results suggest a role for this molecular motor in anxiety control.

  10. An enantioselective synthetic route toward second-generation light-driven rotary molecular motors.

    Science.gov (United States)

    Pijper, Thomas C; Pijper, Dirk; Pollard, Michael M; Dumur, Frédéric; Davey, Stephen G; Meetsma, Auke; Feringa, Ben L

    2010-02-05

    Controlling the unidirectional rotary process of second-generation molecular motors demands access to these motors in their enantiomerically pure form. In this paper, we describe an enantioselective route to three new second-generation light-driven molecular motors. Their synthesis starts with the preparation of an optically active alpha-methoxy-substituted upper-half ketone involving an enzymatic resolution. The subsequent conversion of this ketone to the corresponding hydrazone by treatment with hydrazine led to full racemization. However, conversion to a TBDMS-protected hydrazone by treatment with bis-TBDMS hydrazine, prepared according to a new procedure, proceeds with nearly full retention of the stereochemical integrity. Oxidation of the TBDMS-protected hydrazone and subsequent coupling to a lower-half thioketone followed by recrystallization provided the molecular motors with >99% ee. As these are the first molecular motors that have a methoxy substituent at the stereogenic center, the photochemical and thermal isomerization steps involved in the rotary cycle of one of these new molecules were studied in detail with various spectroscopic techniques.

  11. Mechanical properties of organelles driven by microtubule-dependent molecular motors in living cells.

    Directory of Open Access Journals (Sweden)

    Luciana Bruno

    Full Text Available The organization of the cytoplasm is regulated by molecular motors which transport organelles and other cargoes along cytoskeleton tracks. Melanophores have pigment organelles or melanosomes that move along microtubules toward their minus and plus end by the action of cytoplasmic dynein and kinesin-2, respectively. In this work, we used single particle tracking to characterize the mechanical properties of motor-driven organelles during transport along microtubules. We tracked organelles with high temporal and spatial resolutions and characterized their dynamics perpendicular to the cytoskeleton track. The quantitative analysis of these data showed that the dynamics is due to a spring-like interaction between melanosomes and microtubules in a viscoelastic microenvironment. A model based on a generalized Langevin equation explained these observations and predicted that the stiffness measured for the motor complex acting as a linker between organelles and microtubules is ∼ one order smaller than that determined for motor proteins in vitro. This result suggests that other biomolecules involved in the interaction between motors and organelles contribute to the mechanical properties of the motor complex. We hypothesise that the high flexibility observed for the motor linker may be required to improve the efficiency of the transport driven by multiple copies of motor molecules.

  12. Directed Motion of a Molecular Motor Based Qn the Four-State Model with Unequal Substeps

    Institute of Scientific and Technical Information of China (English)

    WUWei-Xia; ZHANYong; ZHAOTong-Jun; MEIJumPing

    2003-01-01

    A periodic one-dimensional four-state hopping model is proposed. In the model, the substeps between arbitrary adjacent states are unequal, and an explicit solution of the master equation is first obtained for the probability distribution as a function of the time and position for any initial distribution with all the transients included. Next, the transient behaviors in the initial period of time and the characteristic time to reach the steady state for the molecular motor are discussed. Finally, we compare the steady state results to experiments and illustrate qualitatively the kinetic behaviors of a molecular motor under external load F.

  13. O demônio de Maxwell e os motores moleculares

    OpenAIRE

    Goldman, Carla

    2014-01-01

    O transporte ativo nas células é efetuado por certas proteínas, ou motores moleculares como são conhecidas na literatura, capazes de realizar trabalho mecânico em um meio onde predominam forças viscosas. Os mecanismos físicos que regem o movimento dos motores moleculares se inserem no contexto dos processos estocásticos. O modelo padrão introduzido nos anos 90 por Adjari e Prost e por Magnasco para descrever movimento direcionado nesta situação é revisto de maneira pedagógica. Um dos objetivo...

  14. Efficiency bounds of molecular motors under a trade-off figure of merit

    Science.gov (United States)

    Zhang, Yanchao; Huang, Chuankun; Lin, Guoxing; Chen, Jincan

    2017-05-01

    On the basis of the theory of irreversible thermodynamics and an elementary model of the molecular motors converting chemical energy by ATP hydrolysis to mechanical work exerted against an external force, the efficiencies of the molecular motors at two different optimization configurations for trade-off figure of merit representing a best compromise between the useful energy and the lost energy are calculated. The upper and lower bounds for the efficiency at two different optimization configurations are determined. It is found that the optimal efficiencies at the two different optimization configurations are always larger than 1 / 2.

  15. Structured attachment of bacterial molecular motors for defined microflow induction

    Directory of Open Access Journals (Sweden)

    Woerdemann Mike

    2014-01-01

    Full Text Available Bacterial rotational motor complexes that propel flagellated bacteria possess unique properties like their size of a few nanometres and the ability of selfreproduction that have led to various exciting applications including biohybrid nano-machines. One mandatory prerequisite to utilize bacterial nano motors in fluid applications is the ability to transfer force and torque to the fluid, which usually can be achieved by attachment of the bacterial cell to adequate surfaces. Additionally, for optimal transfer of force or torque, precise control of the position down to the single cell level is of utmost importance. Based on a PIV (particle image velocimetry evaluation of the induced flow of single bacteria,we propose and demonstrate attachment of arbitrary patterns of motile bacterial cells in a fast light-based two-step process for the first time to our knowledge. First, these cells are pre-structured by holographic optical tweezers and then attached to a homogeneous, polystyrene-coated surface. In contrast to the few approaches that have been implemented up to now and which rely on pre-structured surfaces, our scheme allows for precise control on a single bacterium level, is versatile, interactive and has low requirements with respect to the surface preparation.

  16. Bounds and phase diagram of efficiency at maximum power for tight-coupling molecular motors.

    Science.gov (United States)

    Tu, Z C

    2013-02-01

    The efficiency at maximum power (EMP) for tight-coupling molecular motors is investigated within the framework of irreversible thermodynamics. It is found that the EMP depends merely on the constitutive relation between the thermodynamic current and force. The motors are classified into four generic types (linear, superlinear, sublinear, and mixed types) according to the characteristics of the constitutive relation, and then the corresponding ranges of the EMP for these four types of molecular motors are obtained. The exact bounds of the EMP are derived and expressed as the explicit functions of the free energy released by the fuel in each motor step. A phase diagram is constructed which clearly shows how the region where the parameters (the load distribution factor and the free energy released by the fuel in each motor step) are located can determine whether the value of the EMP is larger or smaller than 1/2. This phase diagram reveals that motors using ATP as fuel under physiological conditions can work at maximum power with higher efficiency (> 1/2) for a small load distribution factor (< 0.1).

  17. Bidirectional transport by molecular motors: enhanced processivity and response to external forces.

    Science.gov (United States)

    Müller, Melanie J I; Klumpp, Stefan; Lipowsky, Reinhard

    2010-06-02

    Intracellular transport along cytoskeletal filaments is often mediated by two teams of molecular motors that pull on the same cargo and move in opposite directions along the filaments. We have recently shown theoretically that this bidirectional transport can be understood as a stochastic tug-of-war between the two motor teams. Here, we further develop our theory to investigate the experimentally accessible dynamic behavior of cargos transported by strong motors such as kinesin-1 or cytoplasmic dynein. By studying the run and binding times of such a cargo, we show that the properties of biological motors, such as the large ratio of stall/detachment force and the small ratio of superstall backward/forward velocity, are favorable for bidirectional cargo transport, leading to fast motion and enhanced diffusion. In addition, cargo processivity is shown to be strongly enhanced by transport via several molecular motors even if these motors are engaged in a tug-of-war. Finally, we study the motility of a bidirectional cargo under force. Frictional forces arising, e.g., from the viscous cytoplasm, lead to peaks in the velocity distribution, while external forces as exerted, e.g., by an optical trap, lead to hysteresis effects. Our results, in particular our explicit expressions for the cargo binding time and the distance of the peaks in the velocity relation under friction, are directly accessible to in vitro as well as in vivo experiments.

  18. Assembly of bipolar microtubule structures by passive cross-linkers and molecular motors

    Science.gov (United States)

    Johann, D.; Goswami, D.; Kruse, K.

    2016-06-01

    During cell division, sister chromatids are segregated by the mitotic spindle, a bipolar assembly of interdigitating antiparallel polar filaments called microtubules. The spindle contains the midzone, a stable region of overlapping antiparallel microtubules, that is essential for maintaining bipolarity. Although a lot is known about the molecular players involved, the mechanism underlying midzone formation and maintenance is still poorly understood. We study the interaction of polar filaments that are cross-linked by molecular motors moving directionally and by passive cross-linkers diffusing along microtubules. Using a particle-based stochastic model, we find that the interplay of motors and passive cross-linkers can generate a stable finite overlap between a pair of antiparallel polar filaments. We develop a mean-field theory to study this mechanism in detail and investigate the influence of steric interactions between motors and passive cross-linkers on the overlap dynamics. In the presence of interspecies steric interactions, passive cross-linkers mimic the behavior of molecular motors and stable finite overlaps are generated even for non-cross-linking motors. Finally, we develop a mean-field theory for a bundle of aligned polar filaments and show that they can self-organize into a spindlelike pattern. Our work suggests possible ways as to how cells can generate spindle midzones and control their extensions.

  19. Forced desorption of semiflexible polymers, adsorbed and driven by molecular motors

    CERN Document Server

    Chaudhuri, Abhishek

    2014-01-01

    We formulate and characterize a model to describe dynamics of semiflexible polymers in the presence of activity due to motor proteins attached irreversibly to a substrate, and a transverse pulling force acting on one end of the filament. The stochastic binding-unbinding of the motor proteins and their ability to move along the polymer, generates active forces. As the pulling force reaches a threshold value, the polymer eventually desorbs from the substrate. We present a mean field theory that predicts increase in desorption force with polymer bending rigidity, active velocity and processivity of the motor proteins. Performing molecular dynamics simulations of the polymer in presence of a Langevin heat bath, and stochastic motor activity we obtain desorption phase diagrams that show good agreement with theory. With increase in pulling force, the polymer undergoes a first order phase transition from mostly adsorbed to fully desorbed state via a regime of coexistence where the steady state dynamics of the polyme...

  20. A hopping mechanism for cargo transport by molecular motors in crowded microtubules

    CERN Document Server

    Goldman, Carla

    2010-01-01

    Most models designed to study the bidirectional movement of cargos as they are driven by molecular motors rely on the idea that motors of different polarities can be coordinated by external agents if arranged into a motor-cargo complex to perform the necessary work [gross04]. Although these models have provided us with important insights into these phenomena, there are still many unanswered questions regarding the mechanisms through which the movement of the complex takes place on crowded microtubules. For example (i) how does cargo-binding affect motor motility? and in connection with that - (ii) how does the presence of other motors (and also other cargos) on the microtubule affect the motility of the motor-cargo complex? We discuss these questions from a different perspective. The movement of a cargo is conceived here as a hopping process resulting from the transference of cargo between neighboring motors. In the light of this, we examine the conditions under which cargo might display bidirectional movemen...

  1. Adhesion of Photon-Driven Molecular Motors to Surfaces via 1,3-Dipolar Cycloadditions : Effect of Interfacial Interactions on Molecular Motion

    NARCIS (Netherlands)

    Carroll, Gregory T.; London, Gabor; Fernández Landaluce, Tatiana; Rudolf, Petra; Feringa, Ben L.

    2011-01-01

    We report the attachment of altitudinal light-driven molecular motors to surfaces using 1,3-dipolar cycloaddition reactions. Molecular motors were designed containing azide or alkyne groups for attachment to alkyne- or azide-modified surfaces. Surface attachment was characterized by UV-vis, IR, XPS,

  2. Towards Dynamic Control of Wettability by Using Functionalized Altitudinal Molecular Motors on Solid Surfaces

    NARCIS (Netherlands)

    London, Gabor; Chen, Kuang-Yen; Carroll, Gregory T.; Feringa, Ben L.

    2013-01-01

    We report the synthesis of altitudinal molecular motors that contain functional groups in their rotor part. In an approach to achieve dynamic control over the properties of solid surfaces, a hydrophobic perfluorobutyl chain and a relatively hydrophilic cyano group were introduced to the rotor part o

  3. Kinetic analysis of the rotation rate of light-driven unidirectional molecular motors

    NARCIS (Netherlands)

    Klok, Martin; Browne, Wesley R.; Feringa, Ben L.

    2009-01-01

    The combination of a photochemical and a thermal equilibrium in overcrowded alkenes, which is the basis for unidirectional rotation of light-driven molecular rotary motors, is analysed in relation to the actual average rotation rates of such structures. Experimental parameters such as temperature, c

  4. Structural Dynamics of Overcrowded Alkene-Based Molecular Motors during Thermal Isomerization

    NARCIS (Netherlands)

    Cnossen, Arjen; Kistemaker, Jos C. M.; Kojima, Tatsuo; Feringa, Ben L.

    2014-01-01

    Synthetic light-driven rotary molecular motors show complicated structural dynamics during the rotation process. A combination of DFT calculations and various spectroscopic techniques is employed to study the effect of the bridging group in the lower half of the molecule on the conformational dynami

  5. Allosteric Regulation of the Rotational Speed in a Light-Driven Molecular Motor

    NARCIS (Netherlands)

    Faulkner, Adele; van Leeuwen, Thomas; Feringa, Ben L; Wezenberg, Sander J

    2016-01-01

    The rotational speed of an overcrowded alkene-based molecular rotary motor, having an integrated 4,5-diazafluorenyl coordination motif, can be regulated allosterically via the binding of metal ions. DFT calculations have been used to predict the relative speed of rotation of three different (i.e. zi

  6. Design and Construction of a One-Dimensional DNA Track for an Artificial Molecular Motor

    Directory of Open Access Journals (Sweden)

    Suzana Kovacic

    2012-01-01

    Full Text Available DNA is a versatile heteropolymer that shows great potential as a building block for a diverse array of nanostructures. We present here a solution to the problem of designing and synthesizing a DNA-based nanostructure that will serve as the track along which an artificial molecular motor processes. This one-dimensional DNA track exhibits periodically repeating elements that provide specific binding sites for the molecular motor. Besides these binding elements, additional sequences are necessary to label specific regions within the DNA track and to facilitate track construction. Designing an ideal DNA track sequence presents a particular challenge because of the many variable elements that greatly expand the number of potential sequences from which the ideal sequence must be chosen. In order to find a suitable DNA sequence, we have adapted a genetic algorithm which is well suited for a large but sparse search space. This algorithm readily identifies long DNA sequences that include all the necessary elements to both facilitate DNA track construction and to present appropriate binding sites for the molecular motor. We have successfully experimentally incorporated the sequence identified by the algorithm into a long DNA track meeting the criteria for observation of the molecular motor's activity.

  7. Fine tuning of the rotary motion by structural modification in light-driven unidirectional molecular motors

    NARCIS (Netherlands)

    Vicario, J; Walko, M; Meetsma, A; Feringa, Ben L.

    2006-01-01

    The introduction of bulky substituents at the stereogenic center of light-driven second-generation molecular motors results in an acceleration of the speed of rotation. This is due to a more strained structure with elongated C=C bonds and a higher energy level of the ground state relative to the tra

  8. In situ control of polymer helicity with a non-covalently bound photoresponsive molecular motor dopant.

    Science.gov (United States)

    van Leeuwen, Thomas; Heideman, G Henrieke; Zhao, Depeng; Wezenberg, Sander J; Feringa, Ben L

    2017-06-13

    The transfer of chirality from a molecular motor to a dynamic helical polymer via ionic interactions was investigated. A dopant with photoswitchable chirality was able to induce a preferred helicity in a poly(phenylacetylene) polymer and the helicity is inverted upon irradiation. The findings described herein will advance the development of functional and responsive polymeric systems.

  9. Photoinduced Reorganization of Motor-Doped Chiral Liquid Crystals : Bridging Molecular Isomerization and Texture Rotation

    NARCIS (Netherlands)

    Bosco, Alessandro; Jongejan, Mahthild G. M.; Eelkema, Rienk; Katsonis, Nathalie; Lacaze, Ernmanuelle; Ferrarini, Alberta; Feringa, Ben L.; Lacaze, Emmanuelle

    2008-01-01

    We recently reported that the photoisomerization of molecular motors used as chiral dopants in a cholesteric liquid crystal film induces a rotational reorganization which can be observed by optical microscopy and produces the motion of microscopic objects placed on top of the film (Feringa, B. L.;

  10. Towards Dynamic Control of Wettability by Using Functionalized Altitudinal Molecular Motors on Solid Surfaces

    NARCIS (Netherlands)

    London, Gabor; Chen, Kuang-Yen; Carroll, Gregory T.; Feringa, Ben L.

    2013-01-01

    We report the synthesis of altitudinal molecular motors that contain functional groups in their rotor part. In an approach to achieve dynamic control over the properties of solid surfaces, a hydrophobic perfluorobutyl chain and a relatively hydrophilic cyano group were introduced to the rotor part

  11. Characterizing the composition of molecular motors on moving axonal cargo using "cargo mapping" analysis.

    Science.gov (United States)

    Neumann, Sylvia; Campbell, George E; Szpankowski, Lukasz; Goldstein, Lawrence S B; Encalada, Sandra E

    2014-10-30

    Understanding the mechanisms by which molecular motors coordinate their activities to transport vesicular cargoes within neurons requires the quantitative analysis of motor/cargo associations at the single vesicle level. The goal of this protocol is to use quantitative fluorescence microscopy to correlate ("map") the position and directionality of movement of live cargo to the composition and relative amounts of motors associated with the same cargo. "Cargo mapping" consists of live imaging of fluorescently labeled cargoes moving in axons cultured on microfluidic devices, followed by chemical fixation during recording of live movement, and subsequent immunofluorescence (IF) staining of the exact same axonal regions with antibodies against motors. Colocalization between cargoes and their associated motors is assessed by assigning sub-pixel position coordinates to motor and cargo channels, by fitting Gaussian functions to the diffraction-limited point spread functions representing individual fluorescent point sources. Fixed cargo and motor images are subsequently superimposed to plots of cargo movement, to "map" them to their tracked trajectories. The strength of this protocol is the combination of live and IF data to record both the transport of vesicular cargoes in live cells and to determine the motors associated to these exact same vesicles. This technique overcomes previous challenges that use biochemical methods to determine the average motor composition of purified heterogeneous bulk vesicle populations, as these methods do not reveal compositions on single moving cargoes. Furthermore, this protocol can be adapted for the analysis of other transport and/or trafficking pathways in other cell types to correlate the movement of individual intracellular structures with their protein composition. Limitations of this protocol are the relatively low throughput due to low transfection efficiencies of cultured primary neurons and a limited field of view available for

  12. Macroscopic contraction of a gel induced by the integrated motion of light-driven molecular motors.

    Science.gov (United States)

    Li, Quan; Fuks, Gad; Moulin, Emilie; Maaloum, Mounir; Rawiso, Michel; Kulic, Igor; Foy, Justin T; Giuseppone, Nicolas

    2015-02-01

    Making molecular machines that can be useful in the macroscopic world is a challenging long-term goal of nanoscience. Inspired by the protein machinery found in biological systems, and based on the theoretical understanding of the physics of motion at the nanoscale, organic chemists have developed a number of molecules that can produce work by contraction or rotation when triggered by various external chemical or physical stimuli. In particular, basic molecular switches that commute between at least two thermodynamic minima and more advanced molecular motors that behave as dissipative units working far from equilibrium when fuelled with external energy have been reported. However, despite recent progress, the ultimate challenge of coordinating individual molecular motors in a continuous mechanical process that can have a measurable effect at the macroscale has remained elusive. Here, we show that by integrating light-driven unidirectional molecular rotors as reticulating units in a polymer gel, it is possible to amplify their individual motions to achieve macroscopic contraction of the material. Our system uses the incoming light to operate under far-from-equilibrium conditions, and the work produced by the motor in the photostationary state is used to twist the entangled polymer chains up to the collapse of the gel. Our design could be a starting point to integrate nanomotors in metastable materials to store energy and eventually to convert it.

  13. Macroscopic contraction of a gel induced by the integrated motion of light-driven molecular motors

    Science.gov (United States)

    Li, Quan; Fuks, Gad; Moulin, Emilie; Maaloum, Mounir; Rawiso, Michel; Kulic, Igor; Foy, Justin T.; Giuseppone, Nicolas

    2015-02-01

    Making molecular machines that can be useful in the macroscopic world is a challenging long-term goal of nanoscience. Inspired by the protein machinery found in biological systems, and based on the theoretical understanding of the physics of motion at the nanoscale, organic chemists have developed a number of molecules that can produce work by contraction or rotation when triggered by various external chemical or physical stimuli. In particular, basic molecular switches that commute between at least two thermodynamic minima and more advanced molecular motors that behave as dissipative units working far from equilibrium when fuelled with external energy have been reported. However, despite recent progress, the ultimate challenge of coordinating individual molecular motors in a continuous mechanical process that can have a measurable effect at the macroscale has remained elusive. Here, we show that by integrating light-driven unidirectional molecular rotors as reticulating units in a polymer gel, it is possible to amplify their individual motions to achieve macroscopic contraction of the material. Our system uses the incoming light to operate under far-from-equilibrium conditions, and the work produced by the motor in the photostationary state is used to twist the entangled polymer chains up to the collapse of the gel. Our design could be a starting point to integrate nanomotors in metastable materials to store energy and eventually to convert it.

  14. Light-driven rotary molecular motors without point chirality: a minimal design.

    Science.gov (United States)

    Wang, Jun; Oruganti, Baswanth; Durbeej, Bo

    2017-03-08

    A fundamental requirement for achieving photoinduced unidirectional rotary motion about an olefinic bond in a molecular motor is that the potential energy surface of the excited state is asymmetric with respect to clockwise and counterclockwise rotations. In most available light-driven rotary molecular motors, such asymmetry is guaranteed by the presence of a stereocenter. Here, we present non-adiabatic molecular dynamics simulations based on multiconfigurational quantum chemistry to demonstrate that this chiral feature is not essential for inducing unidirectional rotary motion in molecules that incorporate a cyclohexenylidene moiety into a protonated Schiff-base framework. Rather, the simulations show that it is possible to exploit the intrinsic asymmetry of the puckered cyclohexenylidene to control the direction of photoinduced rotation.

  15. Extracting the stepping dynamics of molecular motors in living cells from trajectories of single particles.

    Science.gov (United States)

    Bruno, Augusto; Bruno, Luciana; Levi, Valeria

    2013-01-01

    Molecular motors are responsible of transporting a wide variety of cargos in the cytoplasm. Current efforts are oriented to characterize the biophysical properties of motors in cells with the aim of elucidating the mechanisms of these nanomachines in the complex cellular environment. In this study, we present an algorithm designed to extract motor step sizes and dwell times between steps from trajectories of motors or cargoes driven by motors in cells. The algorithm is based on finding patterns in the trajectory compatible with the behavior expected for a motor step, i.e., a region of confined motion followed by a jump in the position to another region of confined motion with similar characteristics to the previous one. We show that this algorithm allows the analysis of 2D trajectories even if they present complex motion patterns such as active transport interspersed with diffusion and does not require the assumption of a given step size or dwell period. The confidence on the step detection can be easily obtained and allows the evaluation of the confidence of the dwell and step size distributions. To illustrate the possible applications of this algorithm, we analyzed trajectories of myosin-V driven organelles in living cells.

  16. Effective Potential of a Two-State Model for Molecular Motor

    Institute of Scientific and Technical Information of China (English)

    HAN Ying-Rong; ZHAO Tong-Jun; ZHAN-Yong; YAN Wei-Li

    2005-01-01

    We study force generation and motion of molecular motors using a simple two-state model in the paper.Asymmetric and periodic potential is adopted to describe the interaction between motor proteins and filaments that are periodic and polar. The current and the slope of the effective potential as functions of the temperature and transition rates are calculated in the two-state model. The ratio of the slope of the effective potential to the current is also calculated. It is shown that the directed motion of motor proteins is relevant to the effective potential. The slope of the effective potential corresponds to an average force. The non-vanishing force therefore implies that detailed balance is broken in the process of transition between different states.

  17. Analysis of persistence during intracellular actin-based transport mediated by molecular motors

    Energy Technology Data Exchange (ETDEWEB)

    Pallavicini, C; Levi, V; Bruno, L [Departamento de Fisica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires (Argentina); Desposito, M A, E-mail: lbruno@df.uba.a

    2010-09-01

    The displacement of particles or probes in the cell cytoplasm as a function of time is characterized by different anomalous diffusion regimes. The transport of large cargoes, such as organelles, vesicles or large proteins, involves the action of ATP-consuming molecular motors. We investigate the motion of pigment organelles driven by myosin-V motors in Xenopus laevis melanocytes using a high spatio-temporal resolution tracking technique. By analyzing the turning angles ({phi}) of the obtained 2D trajectories as a function of the time lag, we determine the critical time of the transition between anticorrelated and directed motion as the time when the turning angles begin to concentrate around {phi} = 0. We relate this transition with the crossover from subdiffusive to superdiffusive behavior observed in a previous work [5]. We also assayed the properties of the trajectories in cells with inhibited myosin activity, and we can compare the results in the presence and absence of active motors.

  18. Asymptotic Analysis of Microtubule-Based Transport by Multiple Identical Molecular Motors

    CERN Document Server

    McKinley, Scott A; Fricks, John; Kramer, Peter R

    2011-01-01

    We describe a system of stochastic differential equations (SDEs) which model the interaction between processive molecular motors, such as kinesin and dynein, and the biomolecular cargo they tow as part of microtubule-based intracellular transport. We show that the classical experimental environment fits within a parameter regime which is qualitatively distinct from conditions one expects to find in living cells. Through an asymptotic analysis of our system of SDEs, we develop a means for applying in vitro observations of the nonlinear response by motors to forces induced on the attached cargo to make analytical predictions for two parameter regimes that have thus far eluded direct experimental observation: 1) highly viscous in vivo transport and 2) dynamics when multiple identical motors are attached to the cargo and microtubule.

  19. Operations and thermodynamics of an artificial rotary molecular motor in solution.

    Science.gov (United States)

    Moro, Lorenzo; di Giosia, Matteo; Calvaresi, Matteo; Bakalis, Evangelos; Zerbetto, Francesco

    2014-06-23

    A general framework is provided that makes possible the estimation of time-dependent properties of a stochastic system moving far from equilibrium. The process is investigated and discussed in general terms of nonequilibrium thermodynamics. The approach is simple and can be exploited to gain insight into the dynamics of any molecular-level machine. As a case study, the dynamics of an artificial molecular rotary motor, similar to the inversion of a helix, which drives the motor from a metastable state to equilibrium, are examined. The energy path that the motor walks was obtained from the results of atomistic calculations. The motor undergoes unidirectional rotation and its entropy, internal energy, free energy, and net exerted force are given as a function of time, starting from the solution of Smoluchowski's equation. The rather low value of the organization index, that is, the ratio of the work done by the particle against friction during the unidirectional motion per available free energy, reveals that the motion is mainly subject to randomness, and the amount of energy converted to heat due to the directional motion is very small.

  20. A unified phenomenological analysis of the experimental velocity curves in molecular motors.

    Science.gov (United States)

    Ciudad, Aleix; Sancho, J M

    2008-06-14

    We present a unified phenomenological kinetic framework to analyze the experimental data of several motor proteins (either linear or rotatory). This formalism allows us to discriminate the characteristic times of most relevant subprocesses. Explicitly, internal mechanical as well as chemical times are taken into account and joined together in a full-cycle time where effusion, diffusion and chemical rates, viscoelastic friction, and overdamped motion are considered. This approach clarifies the most relevant mechanisms in a particular motor by using the available experimental data of velocity versus external load and substrate concentration. We apply our analysis to three real molecular motors for which enough experimental data are available: the bacterial flagellar motor [Yoshiyuki et al., J. Mol. Biol. 377, 1043 (2003)], conventional kinesin (kinesin-1) [Block et al., Proc. Natl. Acad. Sci. U.S.A. 100, 2351 (2003)], and a RAN polymerase [Abbondanzieril, Nature (London) 438, 460 (2003)]. Moreover, the mechanism of stalling a motor is revised and split into two different concepts (mechanical and chemical stalling) that shed light to the understanding of backstepping in kinesin-1.

  1. Structural and Molecular Basis for Coordination in a Viral DNA Packaging Motor

    Directory of Open Access Journals (Sweden)

    Huzhang Mao

    2016-03-01

    Full Text Available Ring NTPases are a class of ubiquitous molecular motors involved in basic biological partitioning processes. dsDNA viruses encode ring ATPases that translocate their genomes to near-crystalline densities within pre-assembled viral capsids. Here, X-ray crystallography, cryoEM, and biochemical analyses of the dsDNA packaging motor in bacteriophage phi29 show how individual subunits are arranged in a pentameric ATPase ring and suggest how their activities are coordinated to translocate dsDNA. The resulting pseudo-atomic structure of the motor and accompanying functional analyses show how ATP is bound in the ATPase active site; identify two DNA contacts, including a potential DNA translocating loop; demonstrate that a trans-acting arginine finger is involved in coordinating hydrolysis around the ring; and suggest a functional coupling between the arginine finger and the DNA translocating loop. The ability to visualize the motor in action illuminates how the different motor components interact with each other and with their DNA substrate.

  2. Structural and Molecular Basis for Coordination in a Viral DNA Packaging Motor

    Science.gov (United States)

    Reyes-Aldrete, Emilio; Sherman, Michael B.; Woodson, Michael; Atz, Rockney; Grimes, Shelley; Jardine, Paul J.; Morais, Marc C.

    2016-01-01

    SUMMARY Ring NTPases are a class of ubiquitous molecular motors involved in basic biological partitioning processes. dsDNA viruses encode ring ATPases that translocate their genomes to near-crystalline densities within pre-assembled viral capsids. Here, X-ray crystallography, cryoEM, and biochemical analyses of the dsDNA packaging motor in bacteriophage phi29 show how individual subunits are arranged in a pentameric ATPase ring, and suggest how their activities are coordinated to translocate dsDNA. The resulting pseudo-atomic structure of the motor and accompanying functional analyses show how ATP is bound in the ATPase active site; identify two DNA contacts, including a potential DNA translocating loop; demonstrate that a trans-acting arginine finger is involved in coordinating hydrolysis around the ring; and suggest a functional coupling between the arginine finger and the DNA translocating loop. The ability to visualize the motor in action illuminates how the different motor components interact with each other and with their DNA substrate. PMID:26904950

  3. How molecular motors extract order from chaos (a key issues review)

    Science.gov (United States)

    Hoffmann, Peter M.

    2016-03-01

    Molecular motors are the workhorses of living cells. Seemingly by ‘magic’, these molecules are able to complete purposeful tasks while being immersed in a sea of thermal chaos. Here, we review the current understanding of how these machines work, present simple models based on thermal ratchets, discuss implications for statistical physics, and provide an overview of ongoing research in this important and fascinating field of study.

  4. Computational Insight to Improve the Thermal Isomerisation Performance of Overcrowded Alkene-Based Molecular Motors through Structural Redesign.

    Science.gov (United States)

    Oruganti, Baswanth; Wang, Jun; Durbeej, Bo

    2016-11-04

    Synthetic overcrowded alkene-based molecular motors achieve 360° unidirectional rotary motion of one motor half (rotator) relative to the other (stator) through sequential photochemical and thermal isomerisation steps. In order to facilitate and expand the use of these motors for various applications, it is important to investigate ways to increase the rates and efficiencies of the reactions governing the rotary motion. Here, we use computational methods to explore whether the thermal isomerisation performance of some of the fastest available motors of this type can be further improved by reducing the sizes of the motor halves. Presenting three new redesigned motors that combine an indanylidene rotator with a cyclohexadiene, pyran or thiopyran stator, we first use multiconfigurational quantum chemical methods to verify that the photoisomerisations of these motors sustain unidirectional rotary motion. Then, by performing density functional calculations, we identify both stepwise and concerted mechanisms for the thermal isomerisations of the motors and show that the rate-determining free-energy barriers of these processes are up to 25 kJ mol(-1) smaller than those of the original motors. Furthermore, the thermal isomerisations of the redesigned motors proceed in fewer steps. Altogether, the results suggest that the redesigned motors are useful templates for improving the thermal isomerisation performance of existing overcrowded alkene-based motors.

  5. A non-Markov ratchet model of molecular motors: processive movement of single-headed kinesin KIF1A

    Institute of Scientific and Technical Information of China (English)

    Xie Ping; Dou Shuo-Xing; Wang Peng-Ye

    2006-01-01

    A fluctuating ratchet model of non-Markov process is presented to describe the processive movement of molecular motors of single-headed kinesin KIF1A, where the fluctuation perturbation to the local potential is introduced and the detailed ATPase pathway of the motor is included. The theoretical results show good quantitative agreement with the previous experimental ones.

  6. Stochastic dynamics of small ensembles of non-processive molecular motors: the parallel cluster model.

    Science.gov (United States)

    Erdmann, Thorsten; Albert, Philipp J; Schwarz, Ulrich S

    2013-11-07

    Non-processive molecular motors have to work together in ensembles in order to generate appreciable levels of force or movement. In skeletal muscle, for example, hundreds of myosin II molecules cooperate in thick filaments. In non-muscle cells, by contrast, small groups with few tens of non-muscle myosin II motors contribute to essential cellular processes such as transport, shape changes, or mechanosensing. Here we introduce a detailed and analytically tractable model for this important situation. Using a three-state crossbridge model for the myosin II motor cycle and exploiting the assumptions of fast power stroke kinetics and equal load sharing between motors in equivalent states, we reduce the stochastic reaction network to a one-step master equation for the binding and unbinding dynamics (parallel cluster model) and derive the rules for ensemble movement. We find that for constant external load, ensemble dynamics is strongly shaped by the catch bond character of myosin II, which leads to an increase of the fraction of bound motors under load and thus to firm attachment even for small ensembles. This adaptation to load results in a concave force-velocity relation described by a Hill relation. For external load provided by a linear spring, myosin II ensembles dynamically adjust themselves towards an isometric state with constant average position and load. The dynamics of the ensembles is now determined mainly by the distribution of motors over the different kinds of bound states. For increasing stiffness of the external spring, there is a sharp transition beyond which myosin II can no longer perform the power stroke. Slow unbinding from the pre-power-stroke state protects the ensembles against detachment.

  7. Stochastic dynamics of small ensembles of non-processive molecular motors: The parallel cluster model

    Science.gov (United States)

    Erdmann, Thorsten; Albert, Philipp J.; Schwarz, Ulrich S.

    2013-11-01

    Non-processive molecular motors have to work together in ensembles in order to generate appreciable levels of force or movement. In skeletal muscle, for example, hundreds of myosin II molecules cooperate in thick filaments. In non-muscle cells, by contrast, small groups with few tens of non-muscle myosin II motors contribute to essential cellular processes such as transport, shape changes, or mechanosensing. Here we introduce a detailed and analytically tractable model for this important situation. Using a three-state crossbridge model for the myosin II motor cycle and exploiting the assumptions of fast power stroke kinetics and equal load sharing between motors in equivalent states, we reduce the stochastic reaction network to a one-step master equation for the binding and unbinding dynamics (parallel cluster model) and derive the rules for ensemble movement. We find that for constant external load, ensemble dynamics is strongly shaped by the catch bond character of myosin II, which leads to an increase of the fraction of bound motors under load and thus to firm attachment even for small ensembles. This adaptation to load results in a concave force-velocity relation described by a Hill relation. For external load provided by a linear spring, myosin II ensembles dynamically adjust themselves towards an isometric state with constant average position and load. The dynamics of the ensembles is now determined mainly by the distribution of motors over the different kinds of bound states. For increasing stiffness of the external spring, there is a sharp transition beyond which myosin II can no longer perform the power stroke. Slow unbinding from the pre-power-stroke state protects the ensembles against detachment.

  8. Molecular interactions and residues involved in force generation in the T4 viral DNA packaging motor.

    Science.gov (United States)

    Migliori, Amy D; Smith, Douglas E; Arya, Gaurav

    2014-12-12

    Many viruses utilize molecular motors to package their genomes into preformed capsids. A striking feature of these motors is their ability to generate large forces to drive DNA translocation against entropic, electrostatic, and bending forces resisting DNA confinement. A model based on recently resolved structures of the bacteriophage T4 motor protein gp17 suggests that this motor generates large forces by undergoing a conformational change from an extended to a compact state. This transition is proposed to be driven by electrostatic interactions between complementarily charged residues across the interface between the N- and C-terminal domains of gp17. Here we use atomistic molecular dynamics simulations to investigate in detail the molecular interactions and residues involved in such a compaction transition of gp17. We find that although electrostatic interactions between charged residues contribute significantly to the overall free energy change of compaction, interactions mediated by the uncharged residues are equally if not more important. We identify five charged residues and six uncharged residues at the interface that play a dominant role in the compaction transition and also reveal salt bridging, van der Waals, and solvent hydrogen-bonding interactions mediated by these residues in stabilizing the compact form of gp17. The formation of a salt bridge between Glu309 and Arg494 is found to be particularly crucial, consistent with experiments showing complete abrogation in packaging upon Glu309Lys mutation. The computed contributions of several other residues are also found to correlate well with single-molecule measurements of impairments in DNA translocation activity caused by site-directed mutations.

  9. Stochastic dynamics of small ensembles of non-processive molecular motors: the parallel cluster model

    CERN Document Server

    Erdmann, Thorsten; Schwarz, Ulrich S

    2013-01-01

    Non-processive molecular motors have to work together in ensembles in order to generate appreciable levels of force or movement. In skeletal muscle, for example, hundreds of myosin II molecules cooperate in thick filaments. In non-muscle cells, by contrast, small groups with few tens of non-muscle myosin II motors contribute to essential cellular processes such as transport, shape changes or mechanosensing. Here we introduce a detailed and analytically tractable model for this important situation. Using a three-state crossbridge model for the myosin II motor cycle and exploiting the assumptions of fast power stroke kinetics and equal load sharing between motors in equivalent states, we reduce the stochastic reaction network to a one-step master equation for the binding and unbinding dynamics (parallel cluster model) and derive the rules for ensemble movement. We find that for constant external load, ensemble dynamics is strongly shaped by the catch bond character of myosin II, which leads to an increase of th...

  10. Discrete Step Sizes of Molecular Motors Lead to Bimodal Non-Gaussian Velocity Distributions under Force

    Science.gov (United States)

    Vu, Huong T.; Chakrabarti, Shaon; Hinczewski, Michael; Thirumalai, D.

    2016-08-01

    Fluctuations in the physical properties of biological machines are inextricably linked to their functions. Distributions of run lengths and velocities of processive molecular motors, like kinesin-1, are accessible through single-molecule techniques, but rigorous theoretical models for these probabilities are lacking. Here, we derive exact analytic results for a kinetic model to predict the resistive force (F )-dependent velocity [P (v )] and run length [P (n )] distribution functions of generic finitely processive molecular motors. Our theory quantitatively explains the zero force kinesin-1 data for both P (n ) and P (v ) using the detachment rate as the only parameter. In addition, we predict the F dependence of these quantities. At nonzero F , P (v ) is non-Gaussian and is bimodal with peaks at positive and negative values of v , which is due to the discrete step size of kinesin-1. Although the predictions are based on analyses of kinesin-1 data, our results are general and should hold for any processive motor, which walks on a track by taking discrete steps.

  11. Molecular motor-induced instabilities and cross linkers determine biopolymer organization.

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D.; Ziebert, F.; Humphrey, D.; Duggan, C.; Steinbeck, M.; Zimmermann, W.; Kas, J.; Materials Science Division; Univ. of Leipzig; Univ. of Texas at Austin; Univ. Bayreuth

    2007-01-01

    All eukaryotic cells rely on the active self-organization of protein filaments to form a responsive intracellular cytoskeleton. The necessity of motility and reaction to stimuli additionally requires pathways that quickly and reversibly change cytoskeletal organization. While thermally driven order-disorder transitions are, from the viewpoint of physics, the most obvious method for controlling states of organization, the timescales necessary for effective cellular dynamics would require temperatures exceeding the physiologically viable temperature range. We report a mechanism whereby the molecular motor myosin II can cause near-instantaneous order-disorder transitions in reconstituted cytoskeletal actin solutions. When motor-induced filament sliding diminishes, the actin network structure rapidly and reversibly self-organizes into various assemblies. Addition of stable cross linkers was found to alter the architectures of ordered assemblies. These isothermal transitions between dynamic disorder and self-assembled ordered states illustrate that the interplay between passive crosslinking and molecular motor activity plays a substantial role in dynamic cellular organization.

  12. Carbon Nanotube Based Molecular Electronics and Motors: A View from Classical and Quantum Dynamics Simulations

    Science.gov (United States)

    Srivastava, Deepak; Saini, Subhash (Technical Monitor)

    1998-01-01

    The tubular forms of fullerenes popularly known as carbon nanotubes are experimentally produced as single-, multiwall, and rope configurations. The nanotubes and nanoropes have shown to exhibit unusual mechanical and electronic properties. The single wall nanotubes exhibit both semiconducting and metallic behavior. In short undefected lengths they are the known strongest fibers which are unbreakable even when bent in half. Grown in ropes their tensile strength is approximately 100 times greater than steel at only one sixth the weight. Employing large scale classical and quantum molecular dynamics simulations we will explore the use of carbon nanotubes and carbon nanotube junctions in 2-, 3-, and 4-point molecular electronic device components, dynamic strength characterization for compressive, bending and torsional strains, and chemical functionalization for possible use in a nanoscale molecular motor. The above is an unclassified material produced for non-competitive basic research in the nanotechnology area.

  13. Silanization of quartz, silicon and mica surfaces with light-driven molecular motors : construction of surface-bound photo-active nanolayers

    NARCIS (Netherlands)

    London, Gabor; Carroll, Gregory T.; Feringa, Ben L.

    2013-01-01

    The attachment of molecular rotary motors containing triethoxysilane functional groups to quartz, silicon and mica surfaces is described. Motors containing silane coupling agents in their structure form stable molecular layers on quartz and silicon surfaces. Motors attached to these surfaces were fo

  14. On the possibility of the in-cell molecular motors working as cargo moorings only

    CERN Document Server

    Lisowski, Bartosz

    2012-01-01

    Although active transport is considered the most efficient way of depositing materials in the appropriate compartments within living cells, free diffusion remains the energetically cheapest and most widespread determinant of the in-cell dynamics. Here we investigate the hypothesis of cargoes - vesicles or organelles - being transported by the means of free diffusion, limited spatially by the molecular motors. Routinely navigating through ever-changing and unsteady environment, utilizing chemical energy (e.g. from hydrolyzing ATP), as the result they transport cell's crucial components, such as neurotransmitters and organelles. In our model the motor, which we identify with kinesin-1 walking along the microtubule, tethers the cargo in the same manner as a mooring rope attached to a bollard holds a ship from drifting toward the open sea. We study the model behavior in the context of optical trap single molecule experiments, mimicking their procedures in our simulations and investigate how the mechanical propert...

  15. Molecular motors transporting cargos in viscoelastic cytosol: how to beat subdiffusion with a power stroke?

    CERN Document Server

    Goychuk, Igor; Metzler, Ralf

    2013-01-01

    Anomalously slow passive diffusion, $\\langle \\delta x^2(t)\\rangle\\simeq t^{\\alpha}$, with $0<\\alpha<1$, of larger tracers such as messenger RNA and endogenous submicron granules in the cytoplasm of living biological cells has been demonstrated in a number of experiments and has been attributed to the viscoelastic physical nature of the cellular cytoplasm. This finding provokes the question to which extent active intracellular transport is affected by this viscoelastic environment: does the subdiffusion of free submicron cargo such as vesicles and organelles always imply anomalously slow transport by molecular motors such as kinesins, that is, directed transport characterized by a sublinear growth of the mean distance, $\\langle x(t)\\rangle\\simeq t^{\\alpha_{\\rm eff}}$, with $0<\\alpha_{\\rm eff}<1$? Here we study a generic model approach combining the commonly accepted two-state Brownian ratchet model of kinesin motors based on the continuous-state diffusion along microtubule driven by a flashing bind...

  16. The Role of Molecular Microtubule Motors and the Microtubule Cytoskeleton in Stress Granule Dynamics

    Directory of Open Access Journals (Sweden)

    Kristen M. Bartoli

    2011-01-01

    Full Text Available Stress granules (SGs are cytoplasmic foci that appear in cells exposed to stress-induced translational inhibition. SGs function as a triage center, where mRNAs are sorted for storage, degradation, and translation reinitiation. The underlying mechanisms of SGs dynamics are still being characterized, although many key players have been identified. The main components of SGs are stalled 48S preinitiation complexes. To date, many other proteins have also been found to localize in SGs and are hypothesized to function in SG dynamics. Most recently, the microtubule cytoskeleton and associated motor proteins have been demonstrated to function in SG dynamics. In this paper, we will discuss current literature examining the function of microtubules and the molecular microtubule motors in SG assembly, coalescence, movement, composition, organization, and disassembly.

  17. Um modelo simplificado para a dinâmica de motores moleculares

    OpenAIRE

    Ferreira, Luiza Gomes

    2015-01-01

    Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matermáticas, Programa de Pós-Graduação em Física, Florianópolis, 2015. Neste trabalho desenvolvemos um estudo sobre motores moleculares. Um tema muito pesquisado na última década, e que se mostra cada vez mais amplo e interessante. Trabalhamos com modelos estocásticos a fim de modelar o movimento de proteínas motoras de transporte. Os principais exemplos desse tipo de proteína motora são a cinesi...

  18. Directed Motion of a Molecular Motor Based on the Four-State Model with Unequal Substeps

    Institute of Scientific and Technical Information of China (English)

    WU Wei-Xia; ZHAN Yong; ZHAO Tong-Jun; GUAN Rong-Hua; MEI Jun-Ping

    2003-01-01

    A periodic one-dimensional four-state hopping model is proposed. In the model, the substeps betweenarbitrary adjacent states are unequal, and an explicit solution of the master equation is first obtained for the probabilitydistribution as a function of the time and position for any initial distribution with all the transients included. Next, thetransient behaviors in the initial period of time and the characteristic time to reach the steady state for the molecularmotor are discussed. Finally, we compare the steady state results to experiments and illustrate qualitatively the kineticbehaviors of a molecular motor under external load F.

  19. Affinity of molecular interactions in the bacteriophage phi29 DNA packaging motor.

    Science.gov (United States)

    Robinson, Mark A; Wood, Jonathan P A; Capaldi, Stephanie A; Baron, Andrew J; Gell, Christopher; Smith, D Alastair; Stonehouse, Nicola J

    2006-01-01

    DNA packaging in the bacteriophage phi29 involves a molecular motor with protein and RNA components, including interactions between the viral connector protein and molecules of pRNA, both of which form multimeric complexes. Data are presented to demonstrate the higher order assembly of pRNA together with the affinity of pRNA:pRNA and pRNA:connector interactions, which are used to propose a model for motor function. In solution, pRNA can form dimeric and trimeric multimers in a magnesium-dependent manner, with dissociation constants for multimerization in the micromolar range. pRNA:connector binding is also facilitated by the presence of magnesium ions, with a nanomolar apparent dissociation constant for the interaction. From studies with a mutant pRNA, it appears that multimerization of pRNA is not essential for connector binding and it is likely that connector protein is involved in the stabilization of higher order RNA multimers. It is proposed that magnesium ions may promote conformational change that facilitate pRNA:connector interactions, essential for motor function.

  20. Affinity of molecular interactions in the bacteriophage φ29 DNA packaging motor

    Science.gov (United States)

    Robinson, Mark A.; Wood, Jonathan P.A.; Capaldi, Stephanie A.; Baron, Andrew J.; Gell, Christopher; Smith, D. Alastair; Stonehouse, Nicola J.

    2006-01-01

    DNA packaging in the bacteriophage φ29 involves a molecular motor with protein and RNA components, including interactions between the viral connector protein and molecules of pRNA, both of which form multimeric complexes. Data are presented to demonstrate the higher order assembly of pRNA together with the affinity of pRNA:pRNA and pRNA:connector interactions, which are used to propose a model for motor function. In solution, pRNA can form dimeric and trimeric multimers in a magnesium-dependent manner, with dissociation constants for multimerization in the micromolar range. pRNA:connector binding is also facilitated by the presence of magnesium ions, with a nanomolar apparent dissociation constant for the interaction. From studies with a mutant pRNA, it appears that multimerization of pRNA is not essential for connector binding and it is likely that connector protein is involved in the stabilization of higher order RNA multimers. It is proposed that magnesium ions may promote conformational change that facilitate pRNA:connector interactions, essential for motor function. PMID:16714447

  1. A chemically powered unidirectional rotary molecular motor based on a palladium redox cycle

    Science.gov (United States)

    Collins, Beatrice S. L.; Kistemaker, Jos C. M.; Otten, Edwin; Feringa, Ben L.

    2016-09-01

    The conversion of chemical energy to drive directional motion at the molecular level allows biological systems, ranging from subcellular components to whole organisms, to perform a myriad of dynamic functions and respond to changes in the environment. Directional movement has been demonstrated in artificial molecular systems, but the fundamental motif of unidirectional rotary motion along a single-bond rotary axle induced by metal-catalysed transformation of chemical fuels has not been realized, and the challenge is to couple the metal-centred redox processes to stepwise changes in conformation to arrive at a full unidirectional rotary cycle. Here, we present the design of an organopalladium-based motor and the experimental demonstration of a 360° unidirectional rotary cycle using simple chemical fuels. Exploiting fundamental reactivity principles in organometallic chemistry enables control of directional rotation and offers the potential of harnessing the wealth of opportunities offered by transition-metal-based catalytic conversions to drive motion and dynamic functions.

  2. Catalytic properties of Escherichia coli F1-ATPase depleted of endogenous nucleotides.

    Science.gov (United States)

    Senior, A E; Lee, R S; al-Shawi, M K; Weber, J

    1992-09-01

    Nucleotide-depleted Escherichia coli F1 was prepared by the procedure of Wise et al. (1983, Biochem. J. 215, 343-350). This enzyme had high rates of steady-state ATPase and GTPase activity. When "unisite" ATP hydrolysis was measured using an F1/ATP concentration ratio of 10, all of the substoichiometric ATP became bound to the high-affinity catalytic site and none became bound to noncatalytic sites. The association rate constant for ATP binding was 7 x 10(5) M-1 s-1 and the KdATP was 7.9 x 10(-10) M, as compared to values of 3.8 x 10(5) M-1 s-1 and 1.9 x 10(-10) M, respectively, in native (i.e., nucleotide-replete) F1. Rate constants for bound ATP hydrolysis, ATP resynthesis, and P(i) release, and the reaction equilibrium constant, were similar in nucleotide-depleted and native F1. Therefore, we conclude that occupancy of the noncatalytic sites is not required for formation of the high-affinity catalytic site of F1 and has no significant effect on unisite catalysis. In further experiments we looked for the occurrence of inhibitory, catalytic-site-bound MgADP in E. coli F1. Such an entity has been reported for chloroplast and mitochondrial F1. However, our experiments gave no indication for inhibitory MgADP in E. coli F1.

  3. Complementation of Escherichia coli unc mutant strains by chloroplast and cyanobacterial F1-ATPase subunits.

    Science.gov (United States)

    Lill, H; Burkovski, A; Altendorf, K; Junge, W; Engelbrecht, S

    1993-10-04

    The genes encoding the five subunits of the F1 portion of the ATPases from both spinach chloroplasts and the cyanobacterium Synechocystis sp. PCC 6803 were cloned into expression vectors and expressed in Escherichia coli. The recombinant subunits formed inclusion bodies within the cells. Each particular subunit was expressed in the respective unc mutant, each unable to grow on non-fermentable carbon sources. The following subunits restored growth under conditions of oxidative phosphorylation: alpha (both sources, cyanobacterial subunit more than spinach subunit), beta (cyanobacterial subunit only), delta (both spinach and Synechocystis), and epsilon (both sources), whereas no growth was achieved with the gamma subunits from both sources. Despite a high degree of sequence homology the large subunits alpha and beta of spinach and cyanobacterial F1 were not as effective in the substitution of their E. coli counterparts. On the other hand, the two smallest subunits of the E. coli ATPase could be more effectively replaced by their cyanobacterial or chloroplast counterparts, although the sequence identity or even similarity is very low. We attribute these findings to the different roles of these subunits in F1: The large alpha and beta subunits contribute to the catalytic centers of the enzyme, a function rendering them very sensitive to even minor changes. For the smaller delta and epsilon subunits it was sufficient to maintain a certain tertiary structure during evolution, with little emphasis on the conservation of particular amino acids.

  4. E. coli F1-ATPase interacts with a membrane protein component of a proton channel.

    Science.gov (United States)

    Walker, J E; Saraste, M; Gay, N J

    1982-08-26

    The ATP synthases of bacteria, mitochondria and chloroplasts, which use the energy of a transmembrane proton gradient to power the synthesis of ATP, consist of an integral membrane component F0--thought to contain a proton channel--and a catalytic component, F1. To help investigate the way F0 and F1 are coupled, we have sequenced the b-subunit of the Escherichia coli F0, which seems to be the counterpart of a thermophilic bacteria F0 subunit thought to be essential for F1 binding. We report here that its sequence is remarkable, being hydrophobic around the N-terminus and highly charged in the remainder. We propose that the N-terminal segment lies in the membrane and the rest outside. The extramembranous section contains two adjacent stretches of 31 amino acids where the sequence is very similar: in the second of these stretches there is further internal homology. These duplicated stretches of the polypeptide probably fold into two alpha-helices which have many common features able to make contact with F1 subunits. Thus protein b occupies a central position in the enzyme, where it may be involved in proton translocation. It is possibly also important in biosynthetic assembly.

  5. Rotation of subunits during catalysis by Escherichia coli F1-ATPase.

    Science.gov (United States)

    Duncan, T M; Bulygin, V V; Zhou, Y; Hutcheon, M L; Cross, R L

    1995-11-21

    During oxidative and photo-phosphorylation, F0F1-ATP synthases couple the movement of protons down an electrochemical gradient to the synthesis of ATP. One proposed mechanistic feature that has remained speculative is that this coupling process requires the rotation of subunits within F0F1. Guided by a recent, high-resolution structure for bovine F1 [Abrahams, J. P., Leslie, A. G., Lutter, R. & Walker, J. E. (1994) Nature (London) 370, 621-628], we have developed a critical test for rotation of the central gamma subunit relative to the three catalytic beta subunits in soluble F1 from Escherichia coli. In the bovine F1 structure, a specific point of contact between the gamma subunit and one of the three catalytic beta subunits includes positioning of the homolog of E. coli gamma-subunit C87 (gamma C87) close to the beta-subunit 380DELSEED386 sequence. A beta D380C mutation allowed us to induce formation of a specific disulfide bond between beta and gamma C87 in soluble E. coli F1. Formation of the crosslink inactivated beta D380C-F1, and reduction restored full activity. Using a dissociation/reassembly approach with crosslinked beta D380C-F1, we incorporated radiolabeled beta subunits into the two noncrosslinked beta-subunit positions of F1. After reduction of the initial nonradioactive beta-gamma crosslink, only exposure to conditions for catalytic turnover results in similar reactivities of unlabeled and radiolabeled beta subunits with gamma C87 upon reoxidation. The results demonstrate that gamma subunit rotates relative to the beta subunits during catalysis.

  6. Rotation of subunits during catalysis by Escherichia coli F1-ATPase.

    OpenAIRE

    1995-01-01

    During oxidative and photo-phosphorylation, F0F1-ATP synthases couple the movement of protons down an electrochemical gradient to the synthesis of ATP. One proposed mechanistic feature that has remained speculative is that this coupling process requires the rotation of subunits within F0F1. Guided by a recent, high-resolution structure for bovine F1 [Abrahams, J. P., Leslie, A. G., Lutter, R. & Walker, J. E. (1994) Nature (London) 370, 621-628], we have developed a critical test for rotation ...

  7. Thermodynamics and kinetics of the FoF1-ATPase: application of the probability isotherm.

    Science.gov (United States)

    Chapman, Brian; Loiselle, Denis

    2016-02-01

    We use the results of recent publications as vehicles with which to discuss the thermodynamics of the proton-driven mitochondrial F o F1-ATP synthase, focusing particularly on the possibility that there may be dissociation between rotatory steps and ATP synthesis/hydrolysis. Such stoichiometric 'slippage' has been invoked in the literature to explain observed non-ideal behaviour. Numerical solution of the Rate Isotherm (the kinetic equivalent of the more fundamental Probability Isotherm) suggests that such 'slippage' is an unlikely explanation; instead, we suggest that the experimental results may be more consistent with damage to the enzyme caused by its isolation from the biomembrane and its experimental fixation, resulting in non-physiological friction within the enzyme's rotary mechanism. We emphasize the unavoidable constraint of the Second Law as instantiated by the obligatory dissipation of Gibbs Free Energy if the synthase is to operate at anything other than thermodynamic equilibrium. We use further numerical solution of the Rate Isotherm to demonstrate that there is no necessary association of low thermodynamic efficiency with high metabolic rates in a bio-world in which the dominating mechanism of metabolic control is multifactorial enzyme activation.

  8. Are two-station biased random walkers always potential molecular motors?

    Science.gov (United States)

    Bakalis, Evangelos; Zerbetto, Francesco

    2015-01-12

    The short answer to the title question is no. Despite their tremendous complexity, many nanomachines are simply one-dimensional systems undergoing a biased, that is, unidirectional, walk on a two-minima potential energy curve. The initially prepared state, or station, is higher in energy than the final equilibrium state that is reached after overcoming an energy barrier. All chemical reactions comply with this scheme, which does not necessarily imply that a generic chemical reaction is a potential molecular motor. If the barrier is low, the system may walk back and the motion will have a large purely Brownian component. Alternatively, a large distance from the barrier of either of the two stations may introduce a Brownian component. Starting from a general inequality that leverages on the idea that the amount of heat dissipated along the potential energy curve is a good indication of the effectiveness of the biased walk, we provide guidelines for the selection of the features of artificial molecular motors.

  9. The molecular motor Myosin Va interacts with the cilia-centrosomal protein RPGRIP1L

    Science.gov (United States)

    Assis, L. H. P.; Silva-Junior, R. M. P.; Dolce, L. G.; Alborghetti, M. R.; Honorato, R. V.; Nascimento, A. F. Z.; Melo-Hanchuk, T. D.; Trindade, D. M.; Tonoli, C. C. C.; Santos, C. T.; Oliveira, P. S. L.; Larson, R. E.; Kobarg, J.; Espreafico, E. M.; Giuseppe, P. O.; Murakami, M. T.

    2017-01-01

    Myosin Va (MyoVa) is an actin-based molecular motor abundantly found at the centrosome. However, the role of MyoVa at this organelle has been elusive due to the lack of evidence on interacting partners or functional data. Herein, we combined yeast two-hybrid screen, biochemical studies and cellular assays to demonstrate that MyoVa interacts with RPGRIP1L, a cilia-centrosomal protein that controls ciliary signaling and positioning. MyoVa binds to the C2 domains of RPGRIP1L via residues located near or in the Rab11a-binding site, a conserved site in the globular tail domain (GTD) from class V myosins. According to proximity ligation assays, MyoVa and RPGRIP1L can interact near the cilium base in ciliated RPE cells. Furthermore, we showed that RPE cells expressing dominant-negative constructs of MyoVa are mostly unciliated, providing the first experimental evidence about a possible link between this molecular motor and cilia-related processes. PMID:28266547

  10. Silanization of quartz, silicon and mica surfaces with light-driven molecular motors: construction of surface-bound photo-active nanolayers

    OpenAIRE

    London, Gábor; Carroll, Gregory T.; Feringa, Ben L.

    2013-01-01

    The attachment of molecular rotary motors containing triethoxysilane functional groups to quartz, silicon and mica surfaces is described. Motors containing silane coupling agents in their structure form stable molecular layers on quartz and silicon surfaces. Motors attached to these surfaces were found to undergo photochemical and thermal isomerization steps similar to those observed in solution. Additionally, successful formation of molecular "carpets" on atomically flat mica extending micro...

  11. Adhesion of photon-driven molecular motors to surfaces via 1,3-dipolar cycloadditions: effect of interfacial interactions on molecular motion.

    Science.gov (United States)

    Carroll, Gregory T; London, Gábor; Landaluce, Tatiana Fernández; Rudolf, Petra; Feringa, Ben L

    2011-01-25

    We report the attachment of altitudinal light-driven molecular motors to surfaces using 1,3-dipolar cycloaddition reactions. Molecular motors were designed containing azide or alkyne groups for attachment to alkyne- or azide-modified surfaces. Surface attachment was characterized by UV-vis, IR, XPS, and ellipsometry measurements. Surface-bound motors were found to undergo photochemical and thermal isomerizations consistent with unidirectional rotation in solution. Confinement at a surface was found to reduce the rate of the thermal isomerization process. The rate of thermal isomerization was also dependent on the surface coverage of the motors. In solution, changes in the UV-vis signal that accompany thermal isomerization can be fit with a single monoexponential decay. In contrast, thermal isomerization of the surface-bound motors does not follow a single monoexponential decay and was found to fit a biexponential decay. Both one- and two-legged motors were attached to surfaces. The kinetics of thermal isomerization was not affected by the valency of attachment, indicating that the changes in kinetics from solution to surface systems are related to interactions between the surface-bound motors.

  12. Synthetic Molecular Motors: Thermal N Inversion and Directional Photoinduced C=N Bond Rotation of Camphorquinone Imines.

    Science.gov (United States)

    Greb, Lutz; Eichhöfer, Andreas; Lehn, Jean-Marie

    2015-11-23

    The thermal and photochemical E/Z isomerization of camphorquinone-derived imines was studied by a combination of kinetic, structural, and computational methods. The thermal isomerization proceeds by linear N inversion, whereas the photoinduced process occurs through C=N bond rotation with preferred directionality as a result of diastereoisomerism. Thereby, these imines are arguably the simplest example of synthetic molecular motors. The generality of the orthogonal trajectories of the thermal and photochemical pathways allows for the postulation that every suitable chiral imine qualifies, in principle, as a molecular motor driven by light or heat.

  13. Drug Transport Microdevice Mimicking an Idealized Nanoscale Bio-molecular Motor

    Institute of Scientific and Technical Information of China (English)

    Jae Hwan Lee; Ramana M. Pidaparti

    2011-01-01

    Molecular motors are nature's nano-devices and the essential agents of movement that are an integral part of many living organisms.The supramolecular motor,called Nuclear Pore Complex (NPC),controls the transport of all cellular material between the cytoplasm and the nucleus that occurs naturally in biological cells of many organisms.In order to understand the design characteristics of the NPC,we developed a microdevice for drug/fluidic transport mimicking the coarse-grained representation of the NPC geometry through computational fluid dynamic analysis and optimization.Specifically,the role of the central plug in active fluidic/particle transport and passive transport (without central plug) was investigated.Results of flow rate,pressure and velocity profiles obtained from the models indicate that the central plug plays a major role in transport through this biomolecular machine.The results of this investigation show that fluidic transport and flow passages are important factors in designing NPC based nano- and micro-devices for drug delivery.

  14. The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly

    Directory of Open Access Journals (Sweden)

    Paul G. Donlin-Asp

    2017-02-01

    Full Text Available Spinal muscular atrophy (SMA is a motor neuron disease caused by reduced levels of the survival of motor neuron (SMN protein. SMN is part of a multiprotein complex that facilitates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs. SMN has also been found to associate with mRNA-binding proteins, but the nature of this association was unknown. Here, we have employed a combination of biochemical and advanced imaging methods to demonstrate that SMN promotes the molecular interaction between IMP1 protein and the 3′ UTR zipcode region of β-actin mRNA, leading to assembly of messenger ribonucleoprotein (mRNP complexes that associate with the cytoskeleton to facilitate trafficking. We have identified defects in mRNP assembly in cells and tissues from SMA disease models and patients that depend on the SMN Tudor domain and explain the observed deficiency in mRNA localization and local translation, providing insight into SMA pathogenesis as a ribonucleoprotein (RNP-assembly disorder.

  15. Lattice-gas model for active vesicle transport by molecular motors with opposite polarities

    Science.gov (United States)

    Muhuri, Sudipto; Pagonabarraga, Ignacio

    2010-08-01

    We introduce a multispecies lattice-gas model for motor protein driven collective cargo transport on cellular filaments. We use this model to describe and analyze the collective motion of interacting vesicle cargos being carried by oppositely directed molecular motors, moving on a single biofilament. Building on a totally asymmetric exclusion process to characterize the motion of the interacting cargos, we allow for mass exchange with the environment, input, and output at filament boundaries and focus on the role of interconversion rates and how they affect the directionality of the net cargo transport. We quantify the effect of the various different competing processes in terms of nonequilibrium phase diagrams. The interplay of interconversion rates, which allow for flux reversal and evaporation-deposition processes, introduces qualitatively unique features in the phase diagrams. We observe regimes of three-phase coexistence, the possibility of phase re-entrance, and a significant flexibility in how the different phase boundaries shift in response to changes in control parameters. The moving steady-state solutions of this model allows for different possibilities for the spatial distribution of cargo vesicles, ranging from homogeneous distribution of vesicles to polarized distributions, characterized by inhomogeneities or shocks. Current reversals due to internal regulation emerge naturally within the framework of this model. We believe that this minimal model will clarify the understanding of many features of collective vesicle transport, apart from serving as the basis for building more exact quantitative models for vesicle transport relevant to various in vivo situations.

  16. Reaction-diffusion-advection approach to spatially localized treadmilling aggregates of molecular motors

    Science.gov (United States)

    Yochelis, Arik; Bar-On, Tomer; Gov, Nir S.

    2016-04-01

    Unconventional myosins belong to a class of molecular motors that walk processively inside cellular protrusions towards the tips, on top of actin filament. Surprisingly, in addition, they also form retrograde moving self-organized aggregates. The qualitative properties of these aggregates are recapitulated by a mass conserving reaction-diffusion-advection model and admit two distinct families of modes: traveling waves and pulse trains. Unlike the traveling waves that are generated by a linear instability, pulses are nonlinear structures that propagate on top of linearly stable uniform backgrounds. Asymptotic analysis of isolated pulses via a simplified reaction-diffusion-advection variant on large periodic domains, allows to draw qualitative trends for pulse properties, such as the amplitude, width, and propagation speed. The results agree well with numerical integrations and are related to available empirical observations.

  17. Physics of Transport and Traffic Phenomena in Biology: from molecular motors and cells to organisms

    CERN Document Server

    Chowdhury, D; Nishinari, K; Chowdhury, Debashish; Schadschneider, Andreas; Nishinari, Katsuhiro

    2005-01-01

    Traffic-like collective movements are observed at almost all levels of biological systems. Molecular motor proteins like, for example, kinesin and dynein, which are the vehicles of almost all intra-cellular transport in eukayotic cells, sometimes encounter traffic jam that manifests as a disease of the organism. Similarly, traffic jam of collagenase MMP-1, which moves on the collagen fibrils of the extracellular matrix of vertebrates, has also been observed in recent experiments. Traffic-like movements of social insects like ants and termites on trails are, perhaps, more familiar in our everyday life. Experimental, theoretical and computational investigations in the last few years have led to a deeper understanding of the generic or common physical principles involved in these phenomena. In particular, some of the methods of non-equilibrium statistical mechanics, pioneered almost a hundred years ago by Einstein, Langevin and others, turned out to be powerful theoretical tools for quantitaive analysis of model...

  18. The Utilization of Sensori-motor Experiences for Introducing Young Pupils to Molecular Motion: A Report of a Pilot Study.

    Science.gov (United States)

    Hadzigeorgiou, Yannis

    2002-01-01

    Does a sensori-motor experience help a physics student understand the movement of molecules in solids, liquids, and gases? Students aged 9-10 were given either traditional demonstrations of solids, liquids, and gases and the variation of molecular motion with temperature (iconic presentation), or they were involved in physical activities as they…

  19. Driving Unidirectional Molecular Rotary Motors with Visible Light by Intra- And Intermolecular Energy Transfer from Palladium Porphyrin

    NARCIS (Netherlands)

    Cnossen, Arjen; Hou, Lili; Pollard, Michael M.; Wesenhagen, Philana V.; Browne, Wesley R.; Feringa, Ben L.

    2012-01-01

    Driving molecular rotary motors using visible light (530-550 nm) instead of UV light was achieved using palladium tetraphenylporphyrin as a triplet sensitizer. Visible light driven rotation was confirmed by UV/vis absorption, circular dichroism and H-1 NMR spectroscopy and the rotation was confirmed

  20. On the effect of donor and acceptor substituents on the behaviour of light-driven rotary molecular motors

    NARCIS (Netherlands)

    Pollard, Michael M.; Wesenhagen, Philana V.; Pijper, Dirk; Feringa, Ben L.

    2008-01-01

    Light-driven rotary molecular motors based on overcrowded alkenes can be substituted with electron-donating and electron-withdrawing substituents ( R = OMe, Cl and CN) in direct conjugation with the central double bond ( the axis of rotation) without having a significant influence on the rate-limiti

  1. Integrating Bioengineered F1 Motors into Nano-Structured Surfaces

    Science.gov (United States)

    2013-04-23

    Cindy Berrie, Fei Gao. Insertion of a Rigid Structural Element into the Regulatory Domain of the Chloroplast F1-ATPase Gamma Subunit for Rotational...Studies., 15th International Photosynthesis Congress. 2010/08/22 01:00:00, . : , 12/27/2011 3.00 . The Mutation E242K in the chloroplast ATP synthase... chloroplast F1-ATPase gamma subunit for rotational studies. Proceedings of the 15th International Congress on Photosynthesis, 2011, pp.123-126. 2. Colvert

  2. Electric dipole theory and thermodynamics of actomyosin molecular motor in muscle contraction.

    Science.gov (United States)

    Lampinen, Markku J; Noponen, Tuula

    2005-10-21

    Movements in muscles are generated by the myosins which interact with the actin filaments. In this paper we present an electric theory to describe how the chemical energy is first stored in electrostatic form in the myosin system and how it is then released and transformed into work. Due to the longitudinal polarized molecular structure with the negative phosphate group tail, the ATP molecule possesses a large electric dipole moment (p(0)), which makes it an ideal energy source for the electric dipole motor of the actomyosin system. The myosin head contains a large number of strongly restrained water molecules, which makes the ATP-driven electric dipole motor possible. The strongly restrained water molecules can store the chemical energy released by ATP binding and hydrolysis processes in the electric form due to their myosin structure fixed electric dipole moments (p(i)). The decrease in the electric energy is transformed into mechanical work by the rotational movement of the myosin head, which follows from the interaction of the dipoles p(i) with the potential field V(0) of ATP and with the potential field Psi of the actin. The electrical meaning of the hydrolysis reaction is to reduce the dipole moment p(0)-the remaining dipole moment of the adenosine diphosphate (ADP) is appropriately smaller to return the low negative value of the electric energy nearly back to its initial value, enabling the removal of ADP from the myosin head so that the cycling process can be repeated. We derive for the electric energy of the myosin system a general equation, which contains the potential field V(0) with the dipole moment p(0), the dipole moments p(i) and the potential field psi. Using the previously published experimental data for the electric dipole of ATP (p(0) congruent with 230 debye) and for the amount of strongly restrained water molecules (N congruent with 720) in the myosin subfragment (S1), we show that the Gibbs free energy changes of the ATP binding and

  3. Physics of transport and traffic phenomena in biology: from molecular motors and cells to organisms

    Science.gov (United States)

    Chowdhury, Debashish; Schadschneider, Andreas; Nishinari, Katsuhiro

    2005-12-01

    Traffic-like collective movements are observed at almost all levels of biological systems. Molecular motor proteins like, for example, kinesin and dynein, which are the vehicles of almost all intra-cellular transport in eukaryotic cells, sometimes encounter traffic jam that manifests as a disease of the organism. Similarly, traffic jam of collagenase MMP-1, which moves on the collagen fibrils of the extracellular matrix of vertebrates, has also been observed in recent experiments. Novel efforts have been made to utilize some uni-cellular organisms as “micro-transporters”. Traffic-like movements of social insects like ants and termites on trails are, perhaps, more familiar in our everyday life. Experimental, theoretical and computational investigations in the last few years have led to a deeper understanding of the generic or common physical principles involved in these phenomena. In this review we critically examine the current status of our understanding, expose the limitations of the existing methods, mention open challenging questions and speculate on the possible future directions of research in this interdisciplinary area where physics meets not only chemistry and biology but also (nano-)technology.

  4. Reactions driving conformational movements (molecular motors) in gels: conformational and structural chemical kinetics.

    Science.gov (United States)

    Otero, Toribio F

    2017-01-18

    In this perspective the empirical kinetics of conducting polymers exchanging anions and solvent during electrochemical reactions to get dense reactive gels is reviewed. The reaction drives conformational movements of the chains (molecular motors), exchange of ions and solvent with the electrolyte and structural (relaxation, swelling, shrinking and compaction) gel changes. Reaction-driven structural changes are identified and quantified from electrochemical responses. The empirical reaction activation energy (Ea), the reaction coefficient (k) and the reaction orders (α and β) change as a function of the conformational energy variation during the reaction. This conformational energy becomes an empirical magnitude. Ea, k, α and β include and provide quantitative conformational and structural information. The chemical kinetics becomes structural chemical kinetics (SCK) for reactions driving conformational movements of the reactants. The electrochemically stimulated conformational relaxation model describes empirical results and some results from the literature for biochemical reactions. In parallel the development of an emerging technological world of soft, wet, multifunctional and biomimetic tools and anthropomorphic robots driven by reactions of the constitutive material, as in biological organs, can be now envisaged being theoretically supported by the kinetic model.

  5. Parallel computation with molecular-motor-propelled agents in nanofabricated networks.

    Science.gov (United States)

    Nicolau, Dan V; Lard, Mercy; Korten, Till; van Delft, Falco C M J M; Persson, Malin; Bengtsson, Elina; Månsson, Alf; Diez, Stefan; Linke, Heiner; Nicolau, Dan V

    2016-03-01

    The combinatorial nature of many important mathematical problems, including nondeterministic-polynomial-time (NP)-complete problems, places a severe limitation on the problem size that can be solved with conventional, sequentially operating electronic computers. There have been significant efforts in conceiving parallel-computation approaches in the past, for example: DNA computation, quantum computation, and microfluidics-based computation. However, these approaches have not proven, so far, to be scalable and practical from a fabrication and operational perspective. Here, we report the foundations of an alternative parallel-computation system in which a given combinatorial problem is encoded into a graphical, modular network that is embedded in a nanofabricated planar device. Exploring the network in a parallel fashion using a large number of independent, molecular-motor-propelled agents then solves the mathematical problem. This approach uses orders of magnitude less energy than conventional computers, thus addressing issues related to power consumption and heat dissipation. We provide a proof-of-concept demonstration of such a device by solving, in a parallel fashion, the small instance {2, 5, 9} of the subset sum problem, which is a benchmark NP-complete problem. Finally, we discuss the technical advances necessary to make our system scalable with presently available technology.

  6. Silanization of quartz, silicon and mica surfaces with light-driven molecular motors: construction of surface-bound photo-active nanolayers.

    Science.gov (United States)

    London, Gábor; Carroll, Gregory T; Feringa, Ben L

    2013-06-07

    The attachment of molecular rotary motors containing triethoxysilane functional groups to quartz, silicon and mica surfaces is described. Motors containing silane coupling agents in their structure form stable molecular layers on quartz and silicon surfaces. Motors attached to these surfaces were found to undergo photochemical and thermal isomerization steps similar to those observed in solution. Additionally, successful formation of molecular "carpets" on atomically flat mica extending micrometer-sized length scales is presented. These "carpets" were found to undergo morphological changes upon irradiation with UV-light.

  7. Elasticity of a semiflexible filament with a discontinuous tension due to a cross-link or a molecular motor

    OpenAIRE

    Razbin, Mohammadhosein; Benetatos, Panayotis; Zippelius, Annette

    2016-01-01

    We analyze the stretching elasticity of a wormlike chain with a tension discontinuity resulting from a Hookean spring connecting its backbone to a fixed point. The elasticity of isolated semiflexible filaments has been the subject in a significant body of literature, primarily because of its relevance to the mechanics of biological matter. In real systems, however, these filaments are usually part of supramolecular structures involving cross-linkers or molecular motors which cause tension dis...

  8. Visible-Light-Driven Photoisomerization and Increased Rotation Speed of a Molecular Motor Acting as a Ligand in a Ruthenium(II) Complex

    NARCIS (Netherlands)

    Wezenberg, Sander J.; Chen, Kuang-Yen; Feringa, Ben L.

    2015-01-01

    Toward the development of visible-light-driven molecular rotary motors, an overcrowded alkene-based ligand and the corresponding ruthenium(II) complex is presented. In our design, a 4,5-diazafluorenyl coordination motif is directly integrated into the motor function. The photochemical and thermal

  9. Visible-Light-Driven Photoisomerization and Increased Rotation Speed of a Molecular Motor Acting as a Ligand in a Ruthenium(II) Complex

    NARCIS (Netherlands)

    Wezenberg, Sander J; Chen, Kuang-Yen; Feringa, Ben L

    2015-01-01

    Toward the development of visible-light-driven molecular rotary motors, an overcrowded alkene-based ligand and the corresponding ruthenium(II) complex is presented. In our design, a 4,5-diazafluorenyl coordination motif is directly integrated into the motor function. The photochemical and thermal is

  10. Kinetic modeling of molecular motors: pause model and parameter determination from single-molecule experiments

    Science.gov (United States)

    Morin, José A.; Ibarra, Borja; Cao, Francisco J.

    2016-05-01

    Single-molecule manipulation experiments of molecular motors provide essential information about the rate and conformational changes of the steps of the reaction located along the manipulation coordinate. This information is not always sufficient to define a particular kinetic cycle. Recent single-molecule experiments with optical tweezers showed that the DNA unwinding activity of a Phi29 DNA polymerase mutant presents a complex pause behavior, which includes short and long pauses. Here we show that different kinetic models, considering different connections between the active and the pause states, can explain the experimental pause behavior. Both the two independent pause model and the two connected pause model are able to describe the pause behavior of a mutated Phi29 DNA polymerase observed in an optical tweezers single-molecule experiment. For the two independent pause model all parameters are fixed by the observed data, while for the more general two connected pause model there is a range of values of the parameters compatible with the observed data (which can be expressed in terms of two of the rates and their force dependencies). This general model includes models with indirect entry and exit to the long-pause state, and also models with cycling in both directions. Additionally, assuming that detailed balance is verified, which forbids cycling, this reduces the ranges of the values of the parameters (which can then be expressed in terms of one rate and its force dependency). The resulting model interpolates between the independent pause model and the indirect entry and exit to the long-pause state model

  11. Selective cell-surface labeling of the molecular motor protein prestin

    Energy Technology Data Exchange (ETDEWEB)

    McGuire, Ryan M. [Department of Bioengineering, Rice University, Houston, TX 77251 (United States); Silberg, Jonathan J., E-mail: joff@rice.edu [Department of Bioengineering, Rice University, Houston, TX 77251 (United States); Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251 (United States); Pereira, Fred A. [Department of Bioengineering, Rice University, Houston, TX 77251 (United States); Huffington Center on Aging, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States); Raphael, Robert M., E-mail: rraphael@rice.edu [Department of Bioengineering, Rice University, Houston, TX 77251 (United States)

    2011-06-24

    Highlights: {yields} Trafficking to the plasma membrane is required for prestin function. {yields} Biotin acceptor peptide (BAP) was fused to prestin through a transmembrane domain. {yields} BAP-prestin can be metabolically labeled with biotin in HEK293 cells. {yields} Biotin-BAP-prestin allows for selective imaging of fully trafficked prestin. {yields} The biotin-BAP-prestin displays voltage-sensitive activity. -- Abstract: Prestin, a multipass transmembrane protein whose N- and C-termini are localized to the cytoplasm, must be trafficked to the plasma membrane to fulfill its cellular function as a molecular motor. One challenge in studying prestin sequence-function relationships within living cells is separating the effects of amino acid substitutions on prestin trafficking, plasma membrane localization and function. To develop an approach for directly assessing prestin levels at the plasma membrane, we have investigated whether fusion of prestin to a single pass transmembrane protein results in a functional fusion protein with a surface-exposed N-terminal tag that can be detected in living cells. We find that fusion of the biotin-acceptor peptide (BAP) and transmembrane domain of the platelet-derived growth factor receptor (PDGFR) to the N-terminus of prestin-GFP yields a membrane protein that can be metabolically-labeled with biotin, trafficked to the plasma membrane, and selectively detected at the plasma membrane using fluorescently-tagged streptavidin. Furthermore, we show that the addition of a surface detectable tag and a single-pass transmembrane domain to prestin does not disrupt its voltage-sensitive activity.

  12. The molecular motor F-ATP synthase is targeted by the tumoricidal protein HAMLET.

    Science.gov (United States)

    Ho, James; Sielaff, Hendrik; Nadeem, Aftab; Svanborg, Catharina; Grüber, Gerhard

    2015-05-22

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) interacts with multiple tumor cell compartments, affecting cell morphology, metabolism, proteasome function, chromatin structure and viability. This study investigated if these diverse effects of HAMLET might be caused, in part, by a direct effect on the ATP synthase and a resulting reduction in cellular ATP levels. A dose-dependent reduction in cellular ATP levels was detected in A549 lung carcinoma cells, and by confocal microscopy, co-localization of HAMLET with the nucleotide-binding subunits α (non-catalytic) and β (catalytic) of the energy converting F1F0 ATP synthase was detected. As shown by fluorescence correlation spectroscopy, HAMLET binds to the F1 domain of the F1F0 ATP synthase with a dissociation constant (KD) of 20.5μM. Increasing concentrations of the tumoricidal protein HAMLET added to the enzymatically active α3β3γ complex of the F-ATP synthase lowered its ATPase activity, demonstrating that HAMLET binding to the F-ATP synthase effects the catalysis of this molecular motor. Single-molecule analysis was applied to study HAMLET-α3β3γ complex interaction. Whereas the α3β3γ complex of the F-ATP synthase rotated in a counterclockwise direction with a mean rotational rate of 3.8±0.7s(-1), no rotation could be observed in the presence of bound HAMLET. Our findings suggest that direct effects of HAMLET on the F-ATP synthase may inhibit ATP-dependent cellular processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Symmetric linear potential and imperfect Brownian ratchet in molecular motor function

    Institute of Scientific and Technical Information of China (English)

    Li Fang-Zhen; Hu Kuang-Hu; Su Wan-Fang; Chen Yi-Chen

    2005-01-01

    Biomolecular motors are tiny engines that transport materials at the microscopic level within biological cells. In recent years, Elston and Peskin et al have investigated the effect of the elastic properties of the tether that connects the motor to its cargo at the speed of the motor. In this paper we extend their work and present a tether in the form of symmetric linear potential. Our results show that when the driving mechanism is an imperfect Brownian ratchet, the average speed decreases as the stiffness of the tether increases in the limit of large motor diffusion coefficient, which is similar to the results of Elston and Peskin. However, a threshold for the stiffness of the tether connecting the motor to its cargo is found in our model. Only when the tether is stiffer than the threshold can the motor and its cargo function co-operatively, otherwise, the motor and its cargo depart from each other. This result is more realistic than that of the spring model of Elston and Peskin.

  14. Probing single processive molecular motors with high-speed optical tweezers and fluorescence microscopy

    Science.gov (United States)

    Gardini, L.; Pavone, F. S.; Capitanio, M.

    2017-02-01

    Here we present development of optical techniques for the study of single processive myosin motors based on the combination of high-speed optical tweezers force spectroscopy and single molecule fluorescence imaging. Ultrafast force-clamp spectroscopy1 is applied to study the dependence of single chemo-mechanical steps of processive myosin motors on the applied load. On the other hand, single molecule localization through FIONA (Fluorescence Imaging with One Nanometer Accuracy)2, 3 is applied to in vitro motility assay to measure parameters such as the runlength, velocity and step size of single myosin V motors, labeled with Quantum Dots, under unloaded conditions.

  15. Mechanical operation and intersubunit coordination of ring-shaped molecular motors: insights from single-molecule studies.

    Science.gov (United States)

    Liu, Shixin; Chistol, Gheorghe; Bustamante, Carlos

    2014-05-06

    Ring NTPases represent a large and diverse group of proteins that couple their nucleotide hydrolysis activity to a mechanical task involving force generation and some type of transport process in the cell. Because of their shape, these enzymes often operate as gates that separate distinct cellular compartments to control and regulate the passage of chemical species across them. In this manner, ions and small molecules are moved across membranes, biopolymer substrates are segregated between cells or moved into confined spaces, double-stranded nucleic acids are separated into single strands to provide access to the genetic information, and polypeptides are unfolded and processed for recycling. Here we review the recent advances in the characterization of these motors using single-molecule manipulation and detection approaches. We describe the various mechanisms by which ring motors convert chemical energy to mechanical force or torque and coordinate the activities of individual subunits that constitute the ring. We also examine how single-molecule studies have contributed to a better understanding of the structural elements involved in motor-substrate interaction, mechanochemical coupling, and intersubunit coordination. Finally, we discuss how these molecular motors tailor their operation-often through regulation by other cofactors-to suit their unique biological functions.

  16. Computational design of faster rotating second-generation light-driven molecular motors by control of steric effects.

    Science.gov (United States)

    Oruganti, Baswanth; Fang, Changfeng; Durbeej, Bo

    2015-09-07

    We report a systematic computational investigation of the possibility to accelerate the rate-limiting thermal isomerizations of the rotary cycles of synthetic light-driven overcrowded alkene-based molecular motors through modulation of steric interactions. Choosing as a reference system a second-generation motor known to accomplish rotary motion in the MHz regime and using density functional theory methods, we propose a three-step mechanism for the thermal isomerizations of this motor and show that variation of the steric bulkiness of the substituent at the stereocenter can reduce the (already small) free-energy barrier of the rate-determining step by a further 15-17 kJ mol(-1). This finding holds promise for future motors of this kind to reach beyond the MHz regime. Furthermore, we demonstrate and explain why one particular step is kinetically favored by decreasing and another step is kinetically favored by increasing the steric bulkiness of this substituent, and identify a possible back reaction capable of impeding the rotary rate.

  17. Towards a molecular understanding of the apicomplexan actin motor: on a road to novel targets for malaria remedies?

    Energy Technology Data Exchange (ETDEWEB)

    Kumpula, Esa-Pekka [University of Oulu, PO Box 3000, 90014 Oulu (Finland); Helmholtz Centre for Infection Research, Notkestrasse 85, 22607 Hamburg (Germany); German Electron Synchrotron, Notkestrasse 85, 22607 Hamburg (Germany); Kursula, Inari, E-mail: inari.kursula@helmholtz-hzi.de [University of Oulu, PO Box 3000, 90014 Oulu (Finland); Helmholtz Centre for Infection Research, Notkestrasse 85, 22607 Hamburg (Germany); German Electron Synchrotron, Notkestrasse 85, 22607 Hamburg (Germany); University of Bergen, Jonas Lies vei 91, 5009 Bergen (Norway)

    2015-04-16

    In this review, current structural understanding of the apicomplexan glideosome and actin regulation is described. Apicomplexan parasites are the causative agents of notorious human and animal diseases that give rise to considerable human suffering and economic losses worldwide. The most prominent parasites of this phylum are the malaria-causing Plasmodium species, which are widespread in tropical and subtropical regions, and Toxoplasma gondii, which infects one third of the world’s population. These parasites share a common form of gliding motility which relies on an actin–myosin motor. The components of this motor and the actin-regulatory proteins in Apicomplexa have unique features compared with all other eukaryotes. This, together with the crucial roles of these proteins, makes them attractive targets for structure-based drug design. In recent years, several structures of glideosome components, in particular of actins and actin regulators from apicomplexan parasites, have been determined, which will hopefully soon allow the creation of a complete molecular picture of the parasite actin–myosin motor and its regulatory machinery. Here, current knowledge of the function of this motor is reviewed from a structural perspective.

  18. Um modelo de exclusão assimétrico para o transporte de partículas mediado por motores moleculares

    OpenAIRE

    Elisa Thomé Sena

    2008-01-01

    Motores moleculares são proteínas capazes de transportar objetos tais como vesículas, organelas e macromoléculas ao longo do citoesqueleto. Tratam-se de dispositivos bastante interessantes do ponto de vista físico, pois produzem trabalho em um ambiente extremamente ruidoso. Recentemente, diversos experimentos realizados in vivo têm revelado que objetos transportados por motores moleculares ao longo dos microtúbulos apresentam movimento bidirecional. Embora o movimento unidirecional dos motore...

  19. On the possibility to accelerate the thermal isomerizations of overcrowded alkene-based rotary molecular motors with electron-donating or electron-withdrawing substituents.

    Science.gov (United States)

    Oruganti, Baswanth; Durbeej, Bo

    2016-09-01

    We employ computational methods to investigate the possibility of using electron-donating or electron-withdrawing substituents to reduce the free-energy barriers of the thermal isomerizations that limit the rotational frequencies achievable by synthetic overcrowded alkene-based molecular motors. Choosing as reference systems one of the fastest motors known to date and two variants thereof, we consider six new motors obtained by introducing electron-donating methoxy and dimethylamino or electron-withdrawing nitro and cyano substituents in conjugation with the central olefinic bond connecting the two (stator and rotator) motor halves. Performing density functional theory calculations, we then show that electron-donating (but not electron-withdrawing) groups at the stator are able to reduce the already small barriers of the reference motors by up to 18 kJ mol(-1). This result outlines a possible strategy for improving the rotational frequencies of motors of this kind. Furthermore, exploring the origin of the catalytic effect, it is found that electron-donating groups exert a favorable steric influence on the thermal isomerizations, which is not manifested by electron-withdrawing groups. This finding suggests a new mechanism for controlling the critical steric interactions of these motors. Graphical Abstract The introduction of electron-donating groups in one of the fastest rotary molecular motors known to date is found to reduce the free-energy barriers of the thermal steps that limit the rotational frequencies by up to 18 kJ mol(-1).

  20. Molecular classification of amyotrophic lateral sclerosis by unsupervised clustering of gene expression in motor cortex

    NARCIS (Netherlands)

    Aronica, E.; Baas, F.; Iyer, A.; ten Asbroek, A.L.M.A.; Morello, G.; Cavallaro, S.

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease, caused by the loss of motor neurons in the brain and spinal cord. Although 10% of ALS cases are familial (FALS), the majority are sporadic (SALS) and probably associated to a multifactorial e

  1. Quasi-steady State Reduction of Molecular Motor-Based Models of Directed Intermittent Search

    KAUST Repository

    Newby, Jay M.

    2010-02-19

    We present a quasi-steady state reduction of a linear reaction-hyperbolic master equation describing the directed intermittent search for a hidden target by a motor-driven particle moving on a one-dimensional filament track. The particle is injected at one end of the track and randomly switches between stationary search phases and mobile nonsearch phases that are biased in the anterograde direction. There is a finite possibility that the particle fails to find the target due to an absorbing boundary at the other end of the track. Such a scenario is exemplified by the motor-driven transport of vesicular cargo to synaptic targets located on the axon or dendrites of a neuron. The reduced model is described by a scalar Fokker-Planck (FP) equation, which has an additional inhomogeneous decay term that takes into account absorption by the target. The FP equation is used to compute the probability of finding the hidden target (hitting probability) and the corresponding conditional mean first passage time (MFPT) in terms of the effective drift velocity V, diffusivity D, and target absorption rate λ of the random search. The quasi-steady state reduction determines V, D, and λ in terms of the various biophysical parameters of the underlying motor transport model. We first apply our analysis to a simple 3-state model and show that our quasi-steady state reduction yields results that are in excellent agreement with Monte Carlo simulations of the full system under physiologically reasonable conditions. We then consider a more complex multiple motor model of bidirectional transport, in which opposing motors compete in a "tug-of-war", and use this to explore how ATP concentration might regulate the delivery of cargo to synaptic targets. © 2010 Society for Mathematical Biology.

  2. Mixed molecular motor traffic on nucleic acid tracks: models of transcriptional interference and regulation of gene expression

    CERN Document Server

    Bameta, Tripti; Ghanti, Dipanwita; Ghosh, Soumendu

    2015-01-01

    RNA polymerase (RNAP) is molecular machine that polymerizes a RNA molecule, a linear heteropolymer, using a single stranded DNA (ssDNA) as the corresponding template; the sequence of monomers of the RNA is dictated by that of monomers on the ssDNA template. While polymerizing a RNA, the RNAP walks step-by-step on the ssDNA template in a specific direction. Thus, a RNAP can be regarded also as a molecular motor and the sites of start and stop of its walk on the DNA mark the two ends of the genetic message that it transcribes into RNA. Interference of transcription of two overlapping genes is believed to regulate the levels of their expression, i.e., the overall rate of the corresponding RNA synthesis, through suppressive effect of one on the other. Here we model this process as a mixed traffic of two groups of RNAP motors that are characterized by two distinct pairs of start and stop sites. Each group polymerizes identical copies of a RNA while the RNAs polymerized by the two groups are different. These models...

  3. Molecular Motors as the Smallest Motors in the World%世界上最小的马达——分子马达

    Institute of Scientific and Technical Information of China (English)

    陈勇; 周宁; 杜海莲; 冯亚兵; 赵玉芬

    2001-01-01

    @@世界上最小的马达在哪里?就在我们每个人的身体里,它被称为"分子马达"(molecular motor).分子马达是生物体内的一类蛋白质,就像传统的马达一样,它们"燃烧"燃料,做出特定的运动,完成特定的功能.它们是生物体内的"化学能与机械能之间的转换器".某些分子马达也有定子、转子,只不过它们的尺寸都非常小,以纳米为单位,所以被称为世界上最小的马达."生命在于运动",这对于分子马达来说最确切不过了.每个生物体内都有成千上万的分子马达,光合作用需要分子马达,细胞的分裂需要分子马达,肌肉运动也是分子马达在起作用生物体内分子马达无处不在.   

  4. Tug-of-war of molecular motors: the effects of uneven load sharing

    CERN Document Server

    Bouzat, Sebastian; 10.1088/1478-3975/8/6/066010

    2011-01-01

    We analyze theoretically the problem of cargo transport along microtubules by motors of two species with opposite polarities. We consider two different one-dimensional models previously developed in the literature. On the one hand, a quite widespread model which assumes equal force sharing, here referred to as mean field model (MFM). On the other hand, a stochastic model (SM) which considers individual motor-cargo links. We find that in generic situations the MFM predicts larger cargo mean velocity, smaller mean run time and less frequent reversions than the SM. These phenomena are found to be consequences of the load sharing assumptions and can be interpreted in terms the probabilities of the different motility states. We also explore the influence of the viscosity in both models and the role of the stiffness of the motor-cargo links within the SM. Our results show that the mean cargo velocity is independent of the stiffness while the mean run time decreases with such a parameter. We explore the case of symm...

  5. 基于冲击力模型的分子马达动力学分析%Molecular Motor Dynamics in Impact Force Model

    Institute of Scientific and Technical Information of China (English)

    李晨璞; 韩英荣; 展永; 胡金江; 谢革英; 张礼刚; 范虹

    2013-01-01

    With transport characteristics and experiment about molecular motor,an impact force model is established,which conforms Langevin equation.Kinetics of molecular motor transport is analyzed.Molecular motors could take stable stepping motion and effective transport in right impact force combined with noise intensity.Direction of motion of molecular motor is adjusted by direction of impulse force.Though average speed is not zero at different noise intensity,efficient transport of molecular motor ensemble indicates that the system is selective on noise intensity.Average speed of molecular motor ensemble decreases with increasing of load force,the motion even changes its direction as load force is great enough.%从分子马达输运特点和实验现象出发,建立满足朗之万方程的冲击力模型,分析分子马达定向输运的动力学行为.研究发现:在合适的冲击力和噪声强度的共同作用下,分子马达可以稳定的梯跳跃迁运动和有效的输运;分子马达在轨运动的方向由冲击力的方向决定;另外,虽然在不同的噪声强度时平均速度都不为零,但是整个分子马达系综的高效输运对噪声强度有一定的选择性;系综的平均速度随着负载力的增大而减小,甚至会产生反方向的运动.

  6. 分子马达的输运方式研究进展%Research Progress on Transport Ways of the Molecular Motors

    Institute of Scientific and Technical Information of China (English)

    吴魏霞

    2012-01-01

    分子马达(molecularmotor)是生物体细胞内一类具有马达功能的蛋白质大分子,几乎执行了生物体的所有生命活动,其中物质的输运是分子马达的一项重要功能。以往人们一直认为分子马达都是沿着单一轨道单独来输运物质,但随着实验的发展,研究发现分子马达的输运方式多种多样,并且输运过程与多种疾病有关。就分子马达的输运方式最新进展进行综述,阐述分子马达在体内可能的输运方式及与输运过程相关的疾病,最后总结并展望未来。%Molecular motors are protein that perform all tasks vital to the life. Intracellular transport is a very important task. In the past years, people insisted that individual molecular motor transported 'cargo' along single track. But in recent years, various transport ways of molecular motors have been observed from experiments. In addition, research results show that many diseases associate with transport of molecular motors. The new process about transport ways of molecular motors is summarized, including the possible transport behavior patterns of molecular motors and the related diseases. A summary is given and possible future directions are discussed.

  7. Ensemble velocity of non-processive molecular motors with multiple chemical states

    CERN Document Server

    Vilfan, Andrej

    2014-01-01

    We study the ensemble velocity of non-processive motor proteins, described with multiple chemical states. In particular, we discuss the velocity as a function of ATP concentration. Even a simple model which neglects the strain-dependence of transition rates, reverse transition rates and nonlinearities in the elasticity can show interesting functional dependencies, which deviate significantly from the frequently assumed Michaelis-Menten form. We discuss how the oder of events in the duty cycle can be inferred from the measured dependence. The model also predicts the possibility of velocity reversal at a certain ATP concentration if the duty cycle contains several conformational changes of opposite directionalities.

  8. Engineering of a novel Ca²⁺-regulated kinesin molecular motor using a calmodulin dimer linker.

    Science.gov (United States)

    Shishido, Hideki; Maruta, Shinsaku

    2012-06-29

    The kinesin-microtubule system holds great promise as a molecular shuttle device within biochips. However, one current barrier is that such shuttles do not have "on-off" control of their movement. Here we report the development of a novel molecular motor powered by an accelerator and brake system, using a kinesin monomer and a calmodulin (CaM) dimer. The kinesin monomer, K355, was fused with a CaM target peptide (M13 peptide) at the C-terminal part of the neck region (K355-M13). We also prepared CaM dimers using CaM mutants (Q3C), (R86C), or (A147C) and crosslinkers that react with cysteine residues. Following induction of K355-M13 dimerization with CaM dimers, we measured K355-M13 motility and found that it can be reversibly regulated in a Ca(2+)-dependent manner. We also found that velocities of K355-M13 varied depending on the type and crosslink position of the CaM dimer used; crosslink length also had a moderate effect on motility. These results suggest Ca(2+)-dependent dimerization of K355-M13 could be used as a novel molecular shuttle, equipped with an accelerator and brake system, for biochip applications.

  9. Molecular genetics and mechanisms of disease in distal hereditary motor neuropathies: insights directing future genetic studies.

    Science.gov (United States)

    Drew, A P; Blair, I P; Nicholson, G A

    2011-11-01

    The distal hereditary motor neuropathies (dHMNs) are a clinically and genetically heterogeneous group of disorders that primarily affect motor neurons, without significant sensory involvement. New dHMN genes continue to be identified. There are now 11 causative genes described for dHMN, and an additional five genetic loci with unidentified genes. This genetic heterogeneity has further delineated the classification of dHMN, which was previously classified according to mode of inheritance, age at onset, and additional complicating features. Some overlap between phenotypically distinct forms of dHMN is also apparent. The mutated genes identified to-date in dHMN include HSPB1, HSPB8, HSPB3, DCTN1, GARS, PLEKHG5, BSCL2, SETX, IGHMBP2, ATP7A and TRPV4. The pathogenesis of mutations remains to be fully elucidated, however common pathogenic mechanisms are emerging. These include disruption of axonal transport, RNA processing defects, protein aggregation and inclusion body formation, disrupted calcium channel activity, and loss of neuroprotective signalling. Some of these dHMN genes are also mutated in Charcot-Marie-Tooth (CMT) disease and spinal muscular atrophy (SMA). This review examines the growing number of identified dHMN genes, discusses recent insights into the functions of these genes and possible pathogenic mechanisms, and looks at the increasing overlap between dHMN and the other neuropathies CMT2 and SMA.

  10. Mixed molecular motor traffic on nucleic acid tracks: models of transcriptional interference and regulation of gene expression

    CERN Document Server

    Ghosh, Soumendu; Ghanti, Dipanwita; Chowdhury, Debashish

    2015-01-01

    While polymerizing a RNA molecule, a RNA polymerase (RNAP) walks step-by-step on the corresponding single-stranded DNA (ssDNA) template in a specific direction. Thus, a RNAP can be regarded as a molecular motor for which the ssDNA template serves as the track. The sites of start and stop of its walk on the DNA mark the two ends of the genetic message that it transcribes into RNA. Interference of transcription of two overlapping genes can strongly influence the levels of their expression, i.e., the overall rate of the synthesis of the corresponding full-length RNA molecules, through suppressive effect of one on the other. Here we model this process as a mixed traffic of two groups of RNAP motors that are characterized by two distinct pairs of on- and off-ramps. Each group polymerizes identical copies of a RNA while the RNAs polymerized by the two groups are different. These models, which may also be viewed as two interfering totally asymmetric simple exclusion processes, account for all modes of transcriptiona...

  11. Elasticity of a semiflexible filament with a discontinuous tension due to a cross-link or a molecular motor

    CERN Document Server

    Razbin, Mohammadhosein; Zippelius, Annette

    2016-01-01

    We analyze the stretching elasticity of a wormlike chain with a tension discontinuity resulting from a Hookean spring connecting its backbone to a fixed point. The elasticity of isolated semiflexible filaments has been the subject in a significant body of literature, primarily because of its relevance to the mechanics of biological matter. In real systems, however, these filaments are usually part of supramolecular structures involving cross-linkers or molecular motors which cause tension discontinuities. Our model is intended as a minimal structural element incorporating such a discontinuity. We obtain analytical results in the weakly bending limit of the filament, concerning its force-extension relation and the response of the two parts in which the filament is divided by the spring. For a small tension discontinuity, the linear response of the filament extension to this discontinuity strongly depends on the external tension. For large external tension $f$, the spring force contributes a subdominant correct...

  12. Expression of genes encoding F-1-ATPase results in uncoupling of glycolysis from biomass production in Lactococcus lactis

    DEFF Research Database (Denmark)

    Købmann, Brian Jensen; Solem, Christian; Pedersen, M.B.

    2002-01-01

    We studied how the introduction of an additional ATP-consuming reaction affects the metabolic fluxes in Lactococcus lactis. Genes encoding the hydrolytic part of the F-1 domain of the membrane-bound (F1F0) H+-ATPase were expressed from a range of synthetic constitutive promoters. Expression...

  13. Purification, crystallization, and properties of F1-ATPase complexes from the thermoalkaliphilic Bacillus sp. strain TA2.A1.

    Science.gov (United States)

    Stocker, Achim; Keis, Stefanie; Cook, Gregory M; Dimroth, Peter

    2005-11-01

    Recently, we reported the cloning of the atp operon encoding for the F(1)F(0)-ATP synthase from the extremely thermoalkaliphilic bacterium Bacillus sp. strain TA2.A1. In this study, the genes encoding the F(1) moiety of the enzyme complex were cloned from the atp operon into the vector pTrc99A and expressed in Escherichia coli in two variant complexes, F(1)-wt consisting of subunits alpha(3)beta(3)gammadeltaepsilon and F(1)Deltadelta lacking the entire delta-subunit as a prerequisite for overproduction and crystallization trials. Both F(1)-wt and F(1)Deltadelta were successfully overproduced in E. coli and purified in high yield and purity. F(1)Deltadelta was crystallized by micro-batch screening yielding three-dimensional crystals that diffracted to a resolution of 3.1A using a synchrotron radiation source. After establishing cryo and dehydrating conditions, a complete set of diffraction data was collected from a single crystal. No crystals were obtained with F(1)-wt. Data processing of diffraction patterns showed that F(1)Deltadelta crystals belong to the orthorhombic space group P2(1)2(1)2(1) with unit cell parameters of a=121.70, b=174.80, and c=223.50A, alpha, beta, gamma=90.000. The asymmetric unit contained one molecule of bacterial F(1)Deltadelta with a corresponding volume per protein weight (V(M)) of 3.25A(3) Da(-1) and a solvent content of 62.1%. Silver staining of single crystals of F(1)Deltadelta analyzed by SDS-PAGE revealed four bands alpha, beta, gamma, and epsilon with identical M(r)-values as those found in the native F(1)F(0)-ATP synthase isolated from strain TA2.A1 membranes. ATPase assays of F(1)Deltadelta crystals exhibited latent ATP hydrolytic activity that was highly stimulated by lauryldimethylamine oxide, a hallmark of the native enzyme.

  14. Hereditary motor and sensory neuropathies: Understanding molecular pathogenesis could lead to future treatment strategies.

    Science.gov (United States)

    Jerath, Nivedita U; Shy, Michael E

    2015-04-01

    Inherited peripheral neuropathies, like many other degenerative disorders, have been challenging to treat. At this point, there is little specific therapy for the inherited neuropathies other than genetic counseling as well as symptomatic treatment and rehabilitation. In the past, ascorbic acid, progesterone antagonists, and subcutaneous neurotrophin-3 (NT3) injections have demonstrated improvement in animal models of CMT 1A, the most common inherited neuropathy, but have failed to translate any effect in humans. Given the difficulty in treatment, it is important to understand the molecular pathogenesis of hereditary neuropathies in order to strategize potential future therapies. The hereditary neuropathies are in an era of molecular insight and over the past 20 years, more than 78 subtypes of Charcot Marie Tooth disease (CMT) have been identified and extensively studied to understand the biological pathways in greater detail. Next generation molecular sequencing has also improved the diagnosis as well as the understanding of CMT. A greater understanding of the molecular pathways will help pave the way to future therapeutics of CMT. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

  15. Global gene expression analysis of rodent motor neurons following spinal cord injury associates molecular mechanisms with development of post-injury spasticity

    DEFF Research Database (Denmark)

    Wienecke, Jacob; Westerdahl, Ann-Charlotte; Hultborn, Hans;

    2010-01-01

    of endogenous plateau potentials in motor neurons and the development of spasticity after spinalization. To unravel the molecular mechanisms underlying the increased excitability of motor neurons and the return of plateau potentials below a spinal cord injury we investigated changes in gene expression......Spinal cord injury leads to severe problems involving impaired motor, sensory and autonomic functions. After spinal injury there is an initial phase of hypo-reflexia followed by hyper-reflexia, often referred to as spasticity. Previous studies have suggested a relationship between the reappearance...... in this cell population. We adopted a rat tail-spasticity model with a caudal spinal transection that causes a progressive development of spasticity from its onset after two to three weeks until two months post injury. Gene expression changes of fluorescently identified tail motor neurons were studied 21...

  16. Michaelis-Menten at 100 and allosterism at 50: driving molecular motors in a hailstorm with noisy ATPase engines and allosteric transmission.

    Science.gov (United States)

    Chowdhury, Debashish

    2014-01-01

    Cytoskeletal motor proteins move on filamentous tracks by converting input chemical energy that they derive by catalyzing the hydrolysis of ATP. The ATPase site is the analogue of an engine and hydrolysis of ATP is the analogue of burning of chemical fuel. Moreover, the functional role of a segment of the motor is analogous to that of the transmission system of an automobile, which consists of a shaft, gear, clutch, etc. The operation of the engine is intrinsically 'noisy' and the motor faces a molecular 'hailstorm' in the aqueous medium. In this commemorative review, we celebrate the centenary of Michaelis and Menten's landmark paper of 1913 and the golden jubilee of Monod and colleagues classic paper of 1963 by highlighting their relevance with respect to explaining the operational mechanisms of the engine and the transmission system, respectively, of cytoskeletal motors. © 2013 FEBS.

  17. Monte Carlo analysis of neck linker extension in kinesin molecular motors.

    Directory of Open Access Journals (Sweden)

    Matthew L Kutys

    2010-11-01

    Full Text Available Kinesin stepping is thought to involve both concerted conformational changes and diffusive movement, but the relative roles played by these two processes are not clear. The neck linker docking model is widely accepted in the field, but the remainder of the step--diffusion of the tethered head to the next binding site--is often assumed to occur rapidly with little mechanical resistance. Here, we investigate the effect of tethering by the neck linker on the diffusive movement of the kinesin head, and focus on the predicted behavior of motors with naturally or artificially extended neck linker domains. The kinesin chemomechanical cycle was modeled using a discrete-state Markov chain to describe chemical transitions. Brownian dynamics were used to model the tethered diffusion of the free head, incorporating resistive forces from the neck linker and a position-dependent microtubule binding rate. The Brownian dynamics and chemomechanical cycle were coupled to model processive runs consisting of many 8 nm steps. Three mechanical models of the neck linker were investigated: Constant Stiffness (a simple spring, Increasing Stiffness (analogous to a Worm-Like Chain, and Reflecting (negligible stiffness up to a limiting contour length. Motor velocities and run lengths from simulated paths were compared to experimental results from Kinesin-1 and a mutant containing an extended neck linker domain. When tethered by an increasingly stiff spring, the head is predicted to spend an unrealistically short amount of time within the binding zone, and extending the neck is predicted to increase both the velocity and processivity, contrary to experiments. These results suggest that the Worm-Like Chain is not an adequate model for the flexible neck linker domain. The model can be reconciled with experimental data if the neck linker is either much more compliant or much stiffer than generally assumed, or if weak kinesin-microtubule interactions stabilize the diffusing

  18. Motor effect in electron transport through a molecular junction with torsional vibrations

    OpenAIRE

    Pshenichnyuk, Ivan A.; Čížek, Martin

    2010-01-01

    We propose a model for a molecular junction with internal anharmonic torsional vibrations interacting with an electric current. The Wangsness-Bloch-Redfield master equation approach is used to determine the stationary reduced density matrix of the molecule. The dependence of the current, excitation energy and angular momentum of the junction on the applied voltage is studied. Negative differential conductance is observed in the current-voltage characteristics. It is shown that a model with vi...

  19. Engineering of a novel Ca{sup 2+}-regulated kinesin molecular motor using a calmodulin dimer linker

    Energy Technology Data Exchange (ETDEWEB)

    Shishido, Hideki [Department of Bioinformatics, Faculty of Engineering, Soka University, Hachioji, Tokyo 192-8577 (Japan); Maruta, Shinsaku, E-mail: maruta@soka.ac.jp [Department of Bioinformatics, Faculty of Engineering, Soka University, Hachioji, Tokyo 192-8577 (Japan)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer Engineered kinesin-M13 and calmodulin involving single cysteine were prepared. Black-Right-Pointing-Pointer CaM mutant was cross-linked to dimer by bifunctional thiol reactive reagent. Black-Right-Pointing-Pointer Kinesin-M13 was dimerized via CaM dimer in the presence of calcium. Black-Right-Pointing-Pointer Function of the engineered kinesin was regulated by a Ca{sup 2+}-calmodulin dimer linker. -- Abstract: The kinesin-microtubule system holds great promise as a molecular shuttle device within biochips. However, one current barrier is that such shuttles do not have 'on-off' control of their movement. Here we report the development of a novel molecular motor powered by an accelerator and brake system, using a kinesin monomer and a calmodulin (CaM) dimer. The kinesin monomer, K355, was fused with a CaM target peptide (M13 peptide) at the C-terminal part of the neck region (K355-M13). We also prepared CaM dimers using CaM mutants (Q3C), (R86C), or (A147C) and crosslinkers that react with cysteine residues. Following induction of K355-M13 dimerization with CaM dimers, we measured K355-M13 motility and found that it can be reversibly regulated in a Ca{sup 2+}-dependent manner. We also found that velocities of K355-M13 varied depending on the type and crosslink position of the CaM dimer used; crosslink length also had a moderate effect on motility. These results suggest Ca{sup 2+}-dependent dimerization of K355-M13 could be used as a novel molecular shuttle, equipped with an accelerator and brake system, for biochip applications.

  20. Molecular mapping of movement-associated areas in the avian brain: a motor theory for vocal learning origin.

    Science.gov (United States)

    Feenders, Gesa; Liedvogel, Miriam; Rivas, Miriam; Zapka, Manuela; Horita, Haruhito; Hara, Erina; Wada, Kazuhiro; Mouritsen, Henrik; Jarvis, Erich D

    2008-03-12

    Vocal learning is a critical behavioral substrate for spoken human language. It is a rare trait found in three distantly related groups of birds-songbirds, hummingbirds, and parrots. These avian groups have remarkably similar systems of cerebral vocal nuclei for the control of learned vocalizations that are not found in their more closely related vocal non-learning relatives. These findings led to the hypothesis that brain pathways for vocal learning in different groups evolved independently from a common ancestor but under pre-existing constraints. Here, we suggest one constraint, a pre-existing system for movement control. Using behavioral molecular mapping, we discovered that in songbirds, parrots, and hummingbirds, all cerebral vocal learning nuclei are adjacent to discrete brain areas active during limb and body movements. Similar to the relationships between vocal nuclei activation and singing, activation in the adjacent areas correlated with the amount of movement performed and was independent of auditory and visual input. These same movement-associated brain areas were also present in female songbirds that do not learn vocalizations and have atrophied cerebral vocal nuclei, and in ring doves that are vocal non-learners and do not have cerebral vocal nuclei. A compilation of previous neural tracing experiments in songbirds suggests that the movement-associated areas are connected in a network that is in parallel with the adjacent vocal learning system. This study is the first global mapping that we are aware for movement-associated areas of the avian cerebrum and it indicates that brain systems that control vocal learning in distantly related birds are directly adjacent to brain systems involved in movement control. Based upon these findings, we propose a motor theory for the origin of vocal learning, this being that the brain areas specialized for vocal learning in vocal learners evolved as a specialization of a pre-existing motor pathway that controls

  1. Molecular mapping of movement-associated areas in the avian brain: a motor theory for vocal learning origin.

    Directory of Open Access Journals (Sweden)

    Gesa Feenders

    Full Text Available Vocal learning is a critical behavioral substrate for spoken human language. It is a rare trait found in three distantly related groups of birds-songbirds, hummingbirds, and parrots. These avian groups have remarkably similar systems of cerebral vocal nuclei for the control of learned vocalizations that are not found in their more closely related vocal non-learning relatives. These findings led to the hypothesis that brain pathways for vocal learning in different groups evolved independently from a common ancestor but under pre-existing constraints. Here, we suggest one constraint, a pre-existing system for movement control. Using behavioral molecular mapping, we discovered that in songbirds, parrots, and hummingbirds, all cerebral vocal learning nuclei are adjacent to discrete brain areas active during limb and body movements. Similar to the relationships between vocal nuclei activation and singing, activation in the adjacent areas correlated with the amount of movement performed and was independent of auditory and visual input. These same movement-associated brain areas were also present in female songbirds that do not learn vocalizations and have atrophied cerebral vocal nuclei, and in ring doves that are vocal non-learners and do not have cerebral vocal nuclei. A compilation of previous neural tracing experiments in songbirds suggests that the movement-associated areas are connected in a network that is in parallel with the adjacent vocal learning system. This study is the first global mapping that we are aware for movement-associated areas of the avian cerebrum and it indicates that brain systems that control vocal learning in distantly related birds are directly adjacent to brain systems involved in movement control. Based upon these findings, we propose a motor theory for the origin of vocal learning, this being that the brain areas specialized for vocal learning in vocal learners evolved as a specialization of a pre-existing motor

  2. Physics in cell biology: on the physics of biopolymers and molecular motors.

    Science.gov (United States)

    Frey, Erwin

    2002-03-12

    "What is Life?" is the title of a book by Erwin Schrödinger, first published in 1944. This book is a bold attempt to try to understand some of the wonders of life in terms of physics, in particular statistical mechanics. Since the publication of this visionary book, we have seen a revolution in molecular biology complemented by the development of new physical tools like single-molecule spectroscopy. The goal of this article is to highlight some examples where physics can contribute to questions in cell biology. One might hope that through interdisciplinary research one can get closer to answering Schrödinger's fundamental question.

  3. fMRI as a molecular imaging procedure for the functional reorganization of motor systems in chronic stroke

    OpenAIRE

    Lazaridou, Asimina; ASTRAKAS, LOUKAS; Mintzopoulos, Dionyssios; KHANCHICEH, AZADEH; Singhal, Aneesh; Moskowitz, Michael; Rosen, Bruce; Tzika, Aria

    2013-01-01

    Previous brain imaging studies suggest that stroke alters functional connectivity in motor execution networks. Moreover, current understanding of brain plasticity has led to new approaches in stroke rehabilitation. Recent studies showed a significant role of effective coupling of neuronal activity in the SMA (supplementary motor area) and M1 (primary motor cortex) network for motor outcome in patients after stroke. After a subcortical stroke, functional magnetic resonance imaging (fMRI) durin...

  4. Molecular determinants of survival motor neuron (SMN protein cleavage by the calcium-activated protease, calpain.

    Directory of Open Access Journals (Sweden)

    Jennifer L Fuentes

    Full Text Available Spinal muscular atrophy (SMA is a leading genetic cause of childhood mortality, caused by reduced levels of survival motor neuron (SMN protein. SMN functions as part of a large complex in the biogenesis of small nuclear ribonucleoproteins (snRNPs. It is not clear if defects in snRNP biogenesis cause SMA or if loss of some tissue-specific function causes disease. We recently demonstrated that the SMN complex localizes to the Z-discs of skeletal and cardiac muscle sarcomeres, and that SMN is a proteolytic target of calpain. Calpains are implicated in muscle and neurodegenerative disorders, although their relationship to SMA is unclear. Using mass spectrometry, we identified two adjacent calpain cleavage sites in SMN, S192 and F193. Deletion of small motifs in the region surrounding these sites inhibited cleavage. Patient-derived SMA mutations within SMN reduced calpain cleavage. SMN(D44V, reported to impair Gemin2 binding and amino-terminal SMN association, drastically inhibited cleavage, suggesting a role for these interactions in regulating calpain cleavage. Deletion of A188, a residue mutated in SMA type I (A188S, abrogated calpain cleavage, highlighting the importance of this region. Conversely, SMA mutations that interfere with self-oligomerization of SMN, Y272C and SMNΔ7, had no effect on cleavage. Removal of the recently-identified SMN degron (Δ268-294 resulted in increased calpain sensitivity, suggesting that the C-terminus of SMN is important in dictating availability of the cleavage site. Investigation into the spatial determinants of SMN cleavage revealed that endogenous calpains can cleave cytosolic, but not nuclear, SMN. Collectively, the results provide insight into a novel aspect of the post-translation regulation of SMN.

  5. Molecular hydrogen alleviates motor deficits and muscle degeneration in mdx mice.

    Science.gov (United States)

    Hasegawa, Satoru; Ito, Mikako; Fukami, Mayu; Hashimoto, Miki; Hirayama, Masaaki; Ohno, Kinji

    2017-01-01

    Duchenne muscular dystrophy (DMD) is a devastating muscle disease caused by a mutation in DMD encoding dystrophin. Oxidative stress accounts for dystrophic muscle pathologies in DMD. We examined the effects of molecular hydrogen in mdx mice, a model animal for DMD. The pregnant mother started to take supersaturated hydrogen water (>5 ppm) ad libitum from E15.5 up to weaning of the offspring. The mdx mice took supersaturated hydrogen water from weaning until age 10 or 24 weeks when they were sacrificed. Hydrogen water prevented abnormal body mass gain that is commonly observed in mdx mice. Hydrogen improved the spontaneous running distance that was estimated by a counter-equipped running-wheel, and extended the duration on the rota-rod. Plasma creatine kinase activities were decreased by hydrogen at ages 10 and 24 weeks. Hydrogen also decreased the number of central nuclei of muscle fibers at ages 10 and 24 weeks, and immunostaining for nitrotyrosine in gastrocnemius muscle at age 24 weeks. Additionally, hydrogen tended to increase protein expressions of antioxidant glutathione peroxidase 1, as well as anti-apoptotic Bcl-2, in skeletal muscle at age 10 weeks. Although molecular mechanisms of the diverse effects of hydrogen remain to be elucidated, hydrogen potentially improves muscular dystrophy in DMD patients.

  6. From molecular chaperones to membrane motors: through the lens of a mass spectrometrist

    Science.gov (United States)

    2017-01-01

    Twenty-five years ago, we obtained our first mass spectra of molecular chaperones in complex with protein ligands and entered a new field of gas-phase structural biology. It is perhaps now time to pause and reflect, and to ask how many of our initial structure predictions and models derived from mass spectrometry (MS) datasets were correct. With recent advances in structure determination, many of the most challenging complexes that we studied over the years have become tractable by other structural biology approaches enabling such comparisons to be made. Moreover, in the light of powerful new electron microscopy methods, what role is there now for MS? In considering these questions, I will give my personal view on progress and problems as well as my predictions for future directions. PMID:28202679

  7. Taking a molecular motor for a spin: helicase mechanism studied by spin labeling and PELDOR

    Science.gov (United States)

    Constantinescu-Aruxandei, Diana; Petrovic-Stojanovska, Biljana; Schiemann, Olav; Naismith, James H.; White, Malcolm F.

    2016-01-01

    The complex molecular motions central to the functions of helicases have long attracted attention. Protein crystallography has provided transformative insights into these dynamic conformational changes, however important questions about the true nature of helicase configurations during the catalytic cycle remain. Using pulsed EPR (PELDOR or DEER) to measure interdomain distances in solution, we have examined two representative helicases: PcrA from superfamily 1 and XPD from superfamily 2. The data show that PcrA is a dynamic structure with domain movements that correlate with particular functional states, confirming and extending the information gleaned from crystal structures and other techniques. XPD in contrast is shown to be a rigid protein with almost no conformational changes resulting from nucleotide or DNA binding, which is well described by static crystal structures. Our results highlight the complimentary nature of PELDOR to crystallography and the power of its precision in understanding the conformational changes relevant to helicase function. PMID:26657627

  8. Electromagnetic probes of molecular motors in the electron transport chains of mitochondria and chloroplasts

    Science.gov (United States)

    Miller, J. H., Jr.; Nawarathna, D.; Vajrala, V.; Gardner, J.; Widger, W. R.

    2005-12-01

    We report on measurements of harmonics generated by whole cells, mitochondria, and chloroplasts in response to applied sinusoidal electric fields. The frequency- and amplitude-dependence of the induced harmonics exhibit features that correlate with physiological processes. Budding yeast (S. cerevisiae) cells produce numerous harmonics, the amplitudes of which depend strongly on frequency. When the second or third harmonic amplitude is plotted vs. applied frequency, we observe two peaks, around 3 kHz and 12 kHz, which are suppressed by respiratory inhibitors. We observe similar peaks when measuring the harmonic response of B. indicas, a relative of the mitochondrial ancestor. In uncoupled mitochondria, in which most of the electron transport chain is active but the ATP-synthase molecular turbine is inactive, only one (lower frequency) of the two peaks is present. Finally, we find that harmonics generated by chloroplasts depend dramatically on incident light, and vanish in the absence of light.

  9. M(o)TOR of aging: MTOR as a universal molecular hypothalamus.

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2013-07-01

    A recent ground-breaking publication described hypothalamus-driven programmatic aging. As a Russian proverb goes "everything new is well-forgotten old". In 1958, Dilman proposed that aging and its related diseases are programmed by the hypothalamus. This theory, supported by beautiful experiments, remained unnoticed just to be re-discovered recently. Yet, it does not explain all manifestations of aging. And would organism age without hypothalamus? Do sensing pathways such as MTOR (mechanistic Target of Rapamycin) and IKK-beta play a role of a "molecular hypothalamus" in every cell? Are hypothalamus-driven alterations simply a part of quasi-programmed aging manifested by hyperfunction and secondary signal-resistance? Here are some answers.

  10. 分子马达定向运动的合作机制%Cooperative Mechanism in Directed Motion of Molecular Motors

    Institute of Scientific and Technical Information of China (English)

    陈宏斌; 郑志刚

    2012-01-01

    Molecular motors are the frontier topic in biology and physics, and the dynamic mechanism of directed transport attracts much attention. In most cases,molecular motors operate in groups. The interaction and cooperation among motors play an important role in the collective behaviors of molecular motors. The behaviors and mechanism of collective transport of molecular motors are sketched out. Furthermore, two cases are detailedly discussed in which the cooperation among motors is needed for the implementation of directed transport. In the first case, the cooperation impels directed motion under overdamping condition. In the second case, through cooperation molecular motors can gain energy from driving in one direction and do work in the vertical direction,and then cause transversal drift.%分子马达是当前生物学和物理学的前沿课题,其定向运动的动力学机制一直是科学家关注的焦点之一.生物体内的分子马达一般是很多个一起协同工作.相互作用与合作在分子马达集体行为中起了很大作用.本文概述了分子马达合作运动的现象和机制.为进一步阐述合作的意义,本文详细讨论了分子马达必须依靠合作才能实现定向输运的两种情况.第一种,分子马达通过合作,在过阻尼条件下克服不停闪烁的棘齿势,实现了定向运动.第二种,分子马达通过合作,可以将一个方向上输入的驱动能量转化到垂直方向上做功,并产生定向输运.

  11. Elasticity of a semiflexible filament with a discontinuous tension due to a cross-link or a molecular motor

    Science.gov (United States)

    Razbin, Mohammadhosein; Benetatos, Panayotis; Zippelius, Annette

    2016-05-01

    We analyze the stretching elasticity of a wormlike chain with a tension discontinuity resulting from a Hookean spring connecting its backbone to a fixed point. The elasticity of isolated semiflexible filaments has been the subject in a significant body of literature, primarily because of its relevance to the mechanics of biological matter. In real systems, however, these filaments are usually part of supramolecular structures involving cross-linkers or molecular motors, which cause tension discontinuities. Our model is intended as a minimal structural element incorporating such a discontinuity. We obtain analytical results in the weakly bending limit of the filament, concerning its force-extension relation and the response of the two parts in which the filament is divided by the spring. For a small tension discontinuity, the linear response of the filament extension to this discontinuity strongly depends on the external tension. For large external tension f , the spring force contributes a subdominant correction ˜1 /f3 /2 to the well-known ˜1 /√{f } -dependence of the end-to-end extension.

  12. Direct observation of bis(dicarbollyl)nickel conformers in solution by fluorescence spectroscopy: an approach to redox-controlled metallacarborane molecular motors.

    Science.gov (United States)

    Safronov, Alexander V; Shlyakhtina, Natalia I; Everett, Thomas A; VanGordon, Monika R; Sevryugina, Yulia V; Jalisatgi, Satish S; Hawthorne, M Frederick

    2014-10-06

    As a continuation of work on metallacarborane-based molecular motors, the structures of substituted bis(dicarbollyl)nickel complexes in Ni(III) and Ni(IV) oxidation states were investigated in solution by fluorescence spectroscopy. Symmetrically positioned cage-linked pyrene molecules served as fluorescent probes to enable the observation of mixed meso-trans/dl-gauche (pyrene monomer fluorescence) and dl-cis/dl-gauche (intramolecular pyrene excimer fluorescence with residual monomer fluorescence) cage conformations of the nickelacarboranes in the Ni(III) and Ni(IV) oxidation states, respectively. The absence of energetically disfavored conformers in solution--dl-cis in the case of nickel(III) complexes and meso-trans in the case of nickel(IV)--was demonstrated based on spectroscopic data and conformer energy calculations in solution. The conformational persistence observed in solution indicates that bis(dicarbollyl)nickel complexes may provide attractive templates for building electrically driven and/or photodriven molecular motors.

  13. fMRI as a molecular imaging procedure for the functional reorganization of motor systems in chronic stroke

    Science.gov (United States)

    LAZARIDOU, ASIMINA; ASTRAKAS, LOUKAS; MINTZOPOULOS, DIONYSSIOS; KHANCHICEH, AZADEH; SINGHAL, ANEESH; MOSKOWITZ, MICHAEL; ROSEN, BRUCE; TZIKA, ARIA

    2013-01-01

    Previous brain imaging studies suggest that stroke alters functional connectivity in motor execution networks. Moreover, current understanding of brain plasticity has led to new approaches in stroke rehabilitation. Recent studies showed a significant role of effective coupling of neuronal activity in the SMA (supplementary motor area) and M1 (primary motor cortex) network for motor outcome in patients after stroke. After a subcortical stroke, functional magnetic resonance imaging (fMRI) during movement reveals cortical reorganization that is associated with the recovery of function. The aim of the present study was to explore connectivity alterations within the motor-related areas combining motor fMRI with a novel MR-compatible hand-induced robotic device (MR_CHIROD) training. Patients completed training at home and underwent serial MR evaluation at baseline and after 8 weeks of training. Training at home consisted of squeezing a gel exercise ball with the paretic hand at ~75% of maximum strength for 1 h/day, 3 days/week. The fMRI analysis revealed alterations in M1, SMA, PMC (premotor cortex) and Cer (cerebellum) in both stroke patients and healthy controls after the training. Findings of the present study suggest that enhancement of SMA activity could benefit M1 dysfunction in stroke survivors. These results also indicate that connectivity alterations between motor areas might assist the counterbalance of a functionally abnormal M1 in chronic stroke survivors and possibly other patients with motor dysfunction. PMID:23900349

  14. Power Stroke Angular Velocity Profiles of Archaeal A-ATP Synthase Versus Thermophilic and Mesophilic F-ATP Synthase Molecular Motors.

    Science.gov (United States)

    Sielaff, Hendrik; Martin, James; Singh, Dhirendra; Biuković, Goran; Grüber, Gerhard; Frasch, Wayne D

    2016-12-02

    The angular velocities of ATPase-dependent power strokes as a function of the rotational position for the A-type molecular motor A3B3DF, from the Methanosarcina mazei Gö1 A-ATP synthase, and the thermophilic motor α3β3γ, from Geobacillus stearothermophilus (formerly known as Bacillus PS3) F-ATP synthase, are resolved at 5 μs resolution for the first time. Unexpectedly, the angular velocity profile of the A-type was closely similar in the angular positions of accelerations and decelerations to the profiles of the evolutionarily distant F-type motors of thermophilic and mesophilic origins, and they differ only in the magnitude of their velocities. M. mazei A3B3DF power strokes occurred in 120° steps at saturating ATP concentrations like the F-type motors. However, because ATP-binding dwells did not interrupt the 120° steps at limiting ATP, ATP binding to A3B3DF must occur during the catalytic dwell. Elevated concentrations of ADP did not increase dwells occurring 40° after the catalytic dwell. In F-type motors, elevated ADP induces dwells 40° after the catalytic dwell and slows the overall velocity. The similarities in these power stroke profiles are consistent with a common rotational mechanism for A-type and F-type rotary motors, in which the angular velocity is limited by the rotary position at which ATP binding occurs and by the drag imposed on the axle as it rotates within the ring of stator subunits.

  15. Random walks of cytoskeletal motors in open and closed compartments

    NARCIS (Netherlands)

    Lipowsky, R.; Klumpp, S.

    2001-01-01

    Random walks of molecular motors, which bind to and unbind from cytoskeletal filaments, are studied theoretically. The bound and unbound motors undergo directed and nondirected motion, respectively. Motors in open compartments exhibit anomalous drift velocities. Motors in closed compartments generat

  16. Pigment granule translocation in red ovarian chromatophores from the palaemonid shrimp Macrobrachium olfersi (Weigmann, 1836): functional roles for the cytoskeleton and its molecular motors.

    Science.gov (United States)

    Milograna, Sarah Ribeiro; Ribeiro, Márcia Regina; Baqui, Munira Muhammad Abdel; McNamara, John Campbell

    2014-12-01

    The binding of red pigment concentrating hormone (RPCH) to membrane receptors in crustacean chromatophores triggers Ca²⁺/cGMP signaling cascades that activate cytoskeletal motors, driving pigment granule translocation. We investigate the distributions of microfilaments and microtubules and their associated molecular motors, myosin and dynein, by confocal and transmission electron microscopy, evaluating a functional role for the cytoskeleton in pigment translocation using inhibitors of polymer turnover and motor activity in vitro. Microtubules occupy the chromatophore cell extensions whether the pigment granules are aggregated or dispersed. The inhibition of microtubule turnover by taxol induces pigment aggregation and inhibits re-dispersion. Phalloidin-FITC actin labeling, together with tannic acid fixation and ultrastructural analysis, reveals that microfilaments form networks associated with the pigment granules. Actin polymerization induced by jasplaquinolide strongly inhibits RPCH-induced aggregation, causes spontaneous pigment dispersion, and inhibits pigment re-dispersion. Inhibition of actin polymerization by latrunculin-A completely impedes pigment aggregation and re-dispersion. Confocal immunocytochemistry shows that non-muscle myosin II (NMMII) co-localizes mainly with pigment granules while blebbistatin inhibition of NMMII strongly reduces the RPCH response, also inducing spontaneous pigment dispersion. Myosin II and dynein also co-localize with the pigment granules. Inhibition of dynein ATPase by erythro-9-(2-hydroxy-3-nonyl) adenine induces aggregation, inhibits RPCH-triggered aggregation, and inhibits re-dispersion. Granule aggregation and dispersion depend mainly on microfilament integrity although microtubules may be involved. Both cytoskeletal polymers are functional only when subunit turnover is active. Myosin and dynein may be the molecular motors that drive pigment aggregation. These mechanisms of granule translocation in crustacean

  17. 分数阶双头分子马达的欠扩散输运现象%Subdiffusive transport of fractional two-headed molecular motor

    Institute of Scientific and Technical Information of China (English)

    林丽烽; 周兴旺; 马洪

    2013-01-01

    Focusing on the directed transport phenomena of the two-headed molecular motor, we adopt power function as the damping kernel function of general Langevin equation due to the power-law memory characteristics of cytosol in biological cells and present the model of fractional coupling Brownian motor in overdamped condition in this paper. We also discuss the influences of fractional order and coupling factor on the transport speed. From the simulation results there are found the directed transport phenomena and the inverse transport which is not seen in the conventional Brownian motor, in the overdamped fractional coupling Brownian motor. When the noise density is fixed, the generalized stochastic resonance appears when transport speed varies with the fractional order and coupling factor. In particular, the results reveal that the magnitude and direction of the directional flow are controlled by coupling the noise with the interaction force between the two heads, which is the movement characteristic of the two-headed molecular motor in the memory ratchet, rather than of the single-headed motor.%研究具有幂律记忆性的细胞液中双头分子马达的定向输运现象,选取幂函数作为广义Langevin方程的阻尼核函数,建立了分数阶过阻尼耦合Brown马达模型,讨论了阶数及耦合系数对双头分子马达定向输运速度的影响。仿真结果表明,分数阶过阻尼双头分子马达也会产生定向输运现象,并且在某些阶数下会产生整数阶情形所不具有的反向定向流。当噪声强度固定时,输运速度随着阶数以及耦合系数的变化均会出现广义随机共振现象。特别地,研究发现双头分子马达在记忆闪烁棘轮势中具有某些单头分子马达所不具备的运动特性,定向流的大小和方向由噪声与双头间作用力相互耦合控制。

  18. Bacterial Flagellar Motor: A Splendid Molecular Motor%细菌鞭毛马达--一种卓越的分子机器

    Institute of Scientific and Technical Information of China (English)

    邓国宏; 徐启旺; 刘俊康; 丛严广

    2000-01-01

    鞭毛马达(flagellar motor)是一种分子旋转马达,它在细菌鞭毛的结构与功能中起着中心作用.鞭毛马达的结构已基本清楚,主要由Mot A、Mot B、Fli G、Fli M和Fli N 5种蛋白组成定子(stator)和转子(rotor),其驱动力来自于跨膜的H+或Na+流.目前对鞭毛马达的旋转动力学及旋转力矩产生机制已有初步的了解.鞭毛马达可作为研究分子旋转马达的理想模型,对其深入研究将有助于认识生物能量转化利用及细胞运动的机制并具有广泛的生物学意义.

  19. A reconsideration of the link between the energetics of water and of ATP hydrolysis energy in the power strokes of molecular motors in protein structures.

    Science.gov (United States)

    Widdas, Wilfred F

    2008-09-01

    Mechanical energy from oxygen metabolism by mammalian tissues has been studied since 1837. The production of heat by mechanical work was studied by Fick in about 1860. Prior to Fick's work, energetics were revised by Joule's experiments which founded the First Law of Thermodynamics. Fenn in 1923/24 found that frog muscle contractions generated extra heat proportional to the amount of work done in shortening the muscle. This was fully consistent with the Joule, Helmholtz concept used for the First Law of Thermodynamics. The link between the energetics of water and ATP hydrolysis in molecular motors is recommended for reconsideration.

  20. 基于三磷酸腺苷调节的分子马达单向能量跃迁模型%The single-direction energy transition model of molecular motor based on the control of adenosine triphosphate

    Institute of Scientific and Technical Information of China (English)

    李晨璞; 韩英荣; 展永; 谢革英; 胡金江; 张礼刚; 贾利云

    2013-01-01

    分子马达的梯跳运动和在过阻尼溶液中动力学原理尚未揭示清楚,从分子马达输运特点和实验现象出发,构建满足朗之万方程的单向能量跃迁模型,并通过Monte Carlo方法分析了分子马达的随机动力学行为。结果表明,在合适的跃迁能量作用下,分子马达可以利用噪声进行稳定的梯跳运动和有效的输运,但负载力会减弱分子马达系统的输运能力;轨道周期势虽影响分子马达速度的大小但不会改变其运动方向,分子马达运动方向由跃迁能量决定;另外,虽然在不同的噪声强度时平均速度不为零,但是分子马达系统的高效输运对噪声有一定选择性。%The dynamic principle of molecular motor transport in overdamped solution remains unclear. Starting from the transport charac-teristics and phenomenon of the molecular motor system, the single-direction energy transition model is established, which conforms to the Langevin equation, and the stochastic dynamics of molecular motors is analyzed by Monte Carlo simulations. Results show that with the right transition energy, molecular motors could take a stable stepping motion and effective transport by means of the environment noise, and the load force can weaken material transportation of the molecular motor system. The potential field between a molecular motor and its orbit can affect the magnitude of the velocity of motor, but cannot change the direction of the velocity, the direction of motion of the molecular motor therefore is adjusted by the transition energy of the motor. In addition, although the average velocity is not zero for different noise intensities, the efficient transport of a molecular motor system indicates that the system is selective for the noise intensity.

  1. Functional interactions of VirB11 traffic ATPases with VirB4 and VirD4 molecular motors in type IV secretion systems.

    Science.gov (United States)

    Ripoll-Rozada, Jorge; Zunzunegui, Sandra; de la Cruz, Fernando; Arechaga, Ignacio; Cabezón, Elena

    2013-09-01

    Pilus biogenesis and substrate transport by type IV secretion systems require energy, which is provided by three molecular motors localized at the base of the secretion channel. One of these motors, VirB11, belongs to the superfamily of traffic ATPases, which includes members of the type II secretion system and the type IV pilus and archaeal flagellar assembly apparatus. Here, we report the functional interactions between TrwD, the VirB11 homolog of the conjugative plasmid R388, and TrwK and TrwB, the motors involved in pilus biogenesis and DNA transport, respectively. Although these interactions remained standing upon replacement of the traffic ATPase by a homolog from a phylogenetically related conjugative system, namely, TraG of plasmid pKM101, this homolog could not replace the TrwD function for DNA transfer. This result suggests that VirB11 works as a switch between pilus biogenesis and DNA transport and reinforces a mechanistic model in which VirB11 proteins act as traffic ATPases by regulating both events in type IV secretion systems.

  2. Different pathways of molecular pathophysiology underlie cognitive and motor tauopathy phenotypes in transgenic models for Alzheimer's disease and frontotemporal lobar degeneration.

    Science.gov (United States)

    Melis, V; Zabke, C; Stamer, K; Magbagbeolu, M; Schwab, K; Marschall, P; Veh, R W; Bachmann, S; Deiana, S; Moreau, P-H; Davidson, K; Harrington, K A; Rickard, J E; Horsley, D; Garman, R; Mazurkiewicz, M; Niewiadomska, G; Wischik, C M; Harrington, C R; Riedel, G; Theuring, F

    2015-06-01

    A poorly understood feature of the tauopathies is their very different clinical presentations. The frontotemporal lobar degeneration (FTLD) spectrum is dominated by motor and emotional/psychiatric abnormalities, whereas cognitive and memory deficits are prominent in the early stages of Alzheimer's disease (AD). We report two novel mouse models overexpressing different human tau protein constructs. One is a full-length tau carrying a double mutation [P301S/G335D; line 66 (L66)] and the second is a truncated 3-repeat tau fragment which constitutes the bulk of the PHF core in AD corresponding to residues 296-390 fused with a signal sequence targeting it to the endoplasmic reticulum membrane (line 1; L1). L66 has abundant tau pathology widely distributed throughout the brain, with particularly high counts of affected neurons in hippocampus and entorhinal cortex. The pathology is neuroanatomically static and declines with age. Behaviourally, the model is devoid of a higher cognitive phenotype but presents with sensorimotor impairments and motor learning phenotypes. L1 displays a much weaker histopathological phenotype, but shows evidence of neuroanatomical spread and amplification with age that resembles the Braak staging of AD. Behaviourally, the model has minimal motor deficits but shows severe cognitive impairments affecting particularly the rodent equivalent of episodic memory which progresses with advancing age. In both models, tau aggregation can be dissociated from abnormal phosphorylation. The two models make possible the demonstration of two distinct but nevertheless convergent pathways of tau molecular pathogenesis. L1 appears to be useful for modelling the cognitive impairment of AD, whereas L66 appears to be more useful for modelling the motor features of the FTLD spectrum. Differences in clinical presentation of AD-like and FTLD syndromes are therefore likely to be inherent to the respective underlying tauopathy, and are not dependent on presence or absence

  3. A Reconsideration of the Link between the Energetics of Water and of ATP Hydrolysis Energy in the Power Strokes of Molecular Motors in Protein Structures

    Directory of Open Access Journals (Sweden)

    Wilfred F. Widdas

    2008-09-01

    Full Text Available Mechanical energy from oxygen metabolism by mammalian tissues has been studied since 1837. The production of heat by mechanical work was studied by Fick in about 1860. Prior to Fick’s work, energetics were revised by Joule’s experiments which founded the First Law of Thermodynamics. Fenn in 1923/24 found that frog muscle contractions generated extra heat proportional to the amount of work done in shortening the muscle. This was fully consistent with the Joule, Helmholtz concept used for the First Law of Thermodynamics. The link between the energetics of water and ATP hydrolysis in molecular motors is recommended for reconsideration.

  4. Tuning Multiple Motor Travel Via Single Motor Velocity

    Science.gov (United States)

    Xu, Jing; Shu, Zhanyong; King, Stephen J.; Gross, Steven P.

    2012-01-01

    Microtubule-based molecular motors often work in small groups to transport cargos in cells. A key question in understanding transport (and its regulation in vivo) is to identify the sensitivity of multiple-motor-based motion to various single molecule properties. Whereas both single-motor travel distance and microtubule binding rate have been demonstrated to contribute to cargo travel, the role of single-motor velocity is yet to be explored. Here, we recast a previous theoretical study, and make explicit a potential contribution of velocity to cargo travel. We test this possibility experimentally, and demonstrate a strong negative correlation between single-motor velocity and cargo travel for transport driven by two motors. Our study thus discovers a previously unappreciated role of single-motor velocity in regulating multiple-motor transport. PMID:22672518

  5. Chemistry: No turning back for motorized molecules

    Science.gov (United States)

    Clayden, Jonathan

    2016-06-01

    Two molecular motors have been developed that use chemical energy to drive rotational motion in a single direction. The findings bring the prospect of devices powered by such motors a tantalizing step closer. See Letter p.235

  6. Molecular, physiological, and motor performance defects in DMSXL mice carrying >1,000 CTG repeats from the human DM1 locus.

    Directory of Open Access Journals (Sweden)

    Aline Huguet

    Full Text Available Myotonic dystrophy type 1 (DM1 is caused by an unstable CTG repeat expansion in the 3'UTR of the DM protein kinase (DMPK gene. DMPK transcripts carrying CUG expansions form nuclear foci and affect splicing regulation of various RNA transcripts. Furthermore, bidirectional transcription over the DMPK gene and non-conventional RNA translation of repeated transcripts have been described in DM1. It is clear now that this disease may involve multiple pathogenic pathways including changes in gene expression, RNA stability and splicing regulation, protein translation, and micro-RNA metabolism. We previously generated transgenic mice with 45-kb of the DM1 locus and >300 CTG repeats (DM300 mice. After successive breeding and a high level of CTG repeat instability, we obtained transgenic mice carrying >1,000 CTG (DMSXL mice. Here we described for the first time the expression pattern of the DMPK sense transcripts in DMSXL and human tissues. Interestingly, we also demonstrate that DMPK antisense transcripts are expressed in various DMSXL and human tissues, and that both sense and antisense transcripts accumulate in independent nuclear foci that do not co-localize together. Molecular features of DM1-associated RNA toxicity in DMSXL mice (such as foci accumulation and mild missplicing, were associated with high mortality, growth retardation, and muscle defects (abnormal histopathology, reduced muscle strength, and lower motor performances. We have found that lower levels of IGFBP-3 may contribute to DMSXL growth retardation, while increased proteasome activity may affect muscle function. These data demonstrate that the human DM1 locus carrying very large expansions induced a variety of molecular and physiological defects in transgenic mice, reflecting DM1 to a certain extent. As a result, DMSXL mice provide an animal tool to decipher various aspects of the disease mechanisms. In addition, these mice can be used to test the preclinical impact of systemic

  7. Molecular, physiological, and motor performance defects in DMSXL mice carrying >1,000 CTG repeats from the human DM1 locus.

    Science.gov (United States)

    Huguet, Aline; Medja, Fadia; Nicole, Annie; Vignaud, Alban; Guiraud-Dogan, Céline; Ferry, Arnaud; Decostre, Valérie; Hogrel, Jean-Yves; Metzger, Friedrich; Hoeflich, Andreas; Baraibar, Martin; Gomes-Pereira, Mário; Puymirat, Jack; Bassez, Guillaume; Furling, Denis; Munnich, Arnold; Gourdon, Geneviève

    2012-01-01

    Myotonic dystrophy type 1 (DM1) is caused by an unstable CTG repeat expansion in the 3'UTR of the DM protein kinase (DMPK) gene. DMPK transcripts carrying CUG expansions form nuclear foci and affect splicing regulation of various RNA transcripts. Furthermore, bidirectional transcription over the DMPK gene and non-conventional RNA translation of repeated transcripts have been described in DM1. It is clear now that this disease may involve multiple pathogenic pathways including changes in gene expression, RNA stability and splicing regulation, protein translation, and micro-RNA metabolism. We previously generated transgenic mice with 45-kb of the DM1 locus and >300 CTG repeats (DM300 mice). After successive breeding and a high level of CTG repeat instability, we obtained transgenic mice carrying >1,000 CTG (DMSXL mice). Here we described for the first time the expression pattern of the DMPK sense transcripts in DMSXL and human tissues. Interestingly, we also demonstrate that DMPK antisense transcripts are expressed in various DMSXL and human tissues, and that both sense and antisense transcripts accumulate in independent nuclear foci that do not co-localize together. Molecular features of DM1-associated RNA toxicity in DMSXL mice (such as foci accumulation and mild missplicing), were associated with high mortality, growth retardation, and muscle defects (abnormal histopathology, reduced muscle strength, and lower motor performances). We have found that lower levels of IGFBP-3 may contribute to DMSXL growth retardation, while increased proteasome activity may affect muscle function. These data demonstrate that the human DM1 locus carrying very large expansions induced a variety of molecular and physiological defects in transgenic mice, reflecting DM1 to a certain extent. As a result, DMSXL mice provide an animal tool to decipher various aspects of the disease mechanisms. In addition, these mice can be used to test the preclinical impact of systemic therapeutic

  8. The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosin VI Are Required for Clearance of Salmonella Typhimurium by Autophagy.

    Directory of Open Access Journals (Sweden)

    David A Tumbarello

    2015-10-01

    Full Text Available Autophagy plays a key role during Salmonella infection, by eliminating these pathogens following escape into the cytosol. In this process, selective autophagy receptors, including the myosin VI adaptor proteins optineurin and NDP52, have been shown to recognize cytosolic pathogens. Here, we demonstrate that myosin VI and TAX1BP1 are recruited to ubiquitylated Salmonella and play a key role in xenophagy. The absence of TAX1BP1 causes an accumulation of ubiquitin-positive Salmonella, whereas loss of myosin VI leads to an increase in ubiquitylated and LC3-positive bacteria. Our structural studies demonstrate that the ubiquitin-binding site of TAX1BP1 overlaps with the myosin VI binding site and point mutations in the TAX1BP1 zinc finger domains that affect ubiquitin binding also ablate binding to myosin VI. This mutually exclusive binding and the association of TAX1BP1 with LC3 on the outer limiting membrane of autophagosomes may suggest a molecular mechanism for recruitment of this motor to autophagosomes. The predominant role of TAX1BP1, a paralogue of NDP52, in xenophagy is supported by our evolutionary analysis, which demonstrates that functionally intact NDP52 is missing in Xenopus and mice, whereas TAX1BP1 is expressed in all vertebrates analysed. In summary, this work highlights the importance of TAX1BP1 as a novel autophagy receptor in myosin VI-mediated xenophagy. Our study identifies essential new machinery for the autophagy-dependent clearance of Salmonella typhimurium and suggests modulation of myosin VI motor activity as a potential therapeutic target in cellular immunity.

  9. Structure and flexibility of the C-ring in the electromotor of rotary F(0F(1-ATPase of pea chloroplasts.

    Directory of Open Access Journals (Sweden)

    Shai Saroussi

    Full Text Available A ring of 8-15 identical c-subunits is essential for ion-translocation by the rotary electromotor of the ubiquitous F(OF(1-ATPase. Here we present the crystal structure at 3.4Å resolution of the c-ring from chloroplasts of a higher plant (Pisum sativum, determined using a native preparation. The crystal structure was found to resemble that of an (ancestral cyanobacterium. Using elastic network modeling to investigate the ring's eigen-modes, we found five dominant modes of motion that fell into three classes. They revealed the following deformations of the ring: (I ellipsoidal, (II opposite twisting of the luminal circular surface of the ring against the stromal surface, and (III kinking of the hairpin-shaped monomers in the middle, resulting in bending/stretching of the ring. Extension of the elastic network analysis to rings of different c(n-symmetry revealed the same classes of dominant modes as in P. sativum (c(14. We suggest the following functional roles for these classes: The first and third classes of modes affect the interaction of the c-ring with its counterparts in F(O, namely subunits a and bb'. These modes are likely to be involved in ion-translocation and torque generation. The second class of deformation, along with deformations of subunits γ and ε might serve to elastically buffer the torque transmission between F(O and F(1.

  10. Structures of the thermophilic F1-ATPase epsilon subunit suggesting ATP-regulated arm motion of its C-terminal domain in F1.

    Science.gov (United States)

    Yagi, Hiromasa; Kajiwara, Nobumoto; Tanaka, Hideaki; Tsukihara, Tomitake; Kato-Yamada, Yasuyuki; Yoshida, Masasuke; Akutsu, Hideo

    2007-07-03

    The epsilon subunit of bacterial and chloroplast F(o)F(1)-ATP synthases modulates their ATP hydrolysis activity. Here, we report the crystal structure of the ATP-bound epsilon subunit from a thermophilic Bacillus PS3 at 1.9-A resolution. The C-terminal two alpha-helices were folded into a hairpin, sitting on the beta sandwich structure, as reported for Escherichia coli. A previously undescribed ATP binding motif, I(L)DXXRA, recognizes ATP together with three arginine and one glutamate residues. The E. coli epsilon subunit binds ATP in a similar manner, as judged on NMR. We also determined solution structures of the C-terminal domain of the PS3 epsilon subunit and relaxation parameters of the whole molecule by NMR. The two helices fold into a hairpin in the presence of ATP but extend in the absence of ATP. The latter structure has more helical regions and is much more flexible than the former. These results suggest that the epsilon C-terminal domain can undergo an arm-like motion in response to an ATP concentration change and thereby contribute to regulation of F(o)F(1)-ATP synthase.

  11. Construction, expression and characterization of a plasmid-encoded Na(+)-specific ATPase hybrid consisting of Propionigenium modestum F0-ATPase and Escherichia coli F1-ATPase.

    Science.gov (United States)

    Kaim, G; Dimroth, P

    1994-06-01

    The Escherichia coli strain DK8, a deletion mutant lacking the complete unc operon, was transformed with a plasmid containing the genes encoding the a, b, c, delta and part of the alpha subunit of the Na(+)-dependent ATPase of Propionigenium modestum and the genes encoding the alpha, gamma, beta and epsilon subunits of the H(+)-dependent E. coli ATPase. The transformants showed Na(+)-dependent growth on succinate as non-fermentable carbon source. The functionally expressed hybrid ATPase was activated 13-fold at pH 7.5 by the addition of Na+ and inhibited by 1,3-dicyclohexylcarbodiimide, azide and tributyltin chloride. At pH 7.5 and pH 9.0, the hybrid enzyme was protected from inhibition by 1,3-dicyclohexylcarbodiimide in the presence of 50 mM NaCl and 5 mM NaCl, respectively. The hybrid ATPase was reconstituted into proteoliposomes and catalyzed the transport of Na+ upon ATP addition. ATP-dependent fluorescence quenching of 9-amino-6-chloro-2-methoxyacridine proved that the ATPase hybrid was able to pump protons in the absence of Na+. Furthermore, ATP synthesis could be measured under conditions where a valinomycin-mediated K+ diffusion potential (delta psi) and a Na+ concentration gradient (delta p Na+) were imposed.

  12. Mutagenesis of residue betaArg-246 in the phosphate-binding subdomain of catalytic sites of Escherichia coli F1-ATPase.

    Science.gov (United States)

    Ahmad, Zulfiqar; Senior, Alan E

    2004-07-23

    Residues responsible for phosphate binding in F(1)F(0)-ATP synthase catalytic sites are of significant interest because phosphate binding is believed linked to proton gradient-driven subunit rotation. From x-ray structures, a phosphate-binding subdomain is evident in catalytic sites, with conserved betaArg-246 in a suitable position to bind phosphate. Mutations betaR246Q, betaR246K, and betaR246A in Escherichia coli were found to impair oxidative phosphorylation and to reduce ATPase activity of purified F(1) by 100-fold. In contrast to wild type, ATPase of mutants was not inhibited by MgADP-fluoroaluminate or MgADP-fluoroscandium, showing the Arg side chain is required for wild-type transition state formation. Whereas 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) inhibited wild-type ATPase essentially completely, ATPase in mutants was inhibited maximally by approximately 50%, although reaction still occurred at residue betaTyr-297, proximal to betaArg-246 in the phosphate-binding pocket. Inhibition characteristics supported the conclusion that NBD-Cl reacts in betaE (empty) catalytic sites, as shown previously by x-ray structure analysis. Phosphate protected against NBD-Cl inhibition in wild type but not in mutants. The results show that phosphate can bind in the betaE catalytic site of E. coli F(1) and that betaArg-246 is an important phosphate-binding residue.

  13. New insights into the function of a versatile class of membrane molecular motors from studies of Myxococcus xanthus surface (gliding motility

    Directory of Open Access Journals (Sweden)

    Tâm Mignot

    2017-03-01

    Full Text Available Cell motility is a central function of living cells, as it empowers colonization of new environmental niches, cooperation, and development of multicellular organisms. This process is achieved by complex yet precise energy-consuming machineries in both eukaryotes and bacteria. Bacteria move on surfaces using extracellular appendages such as flagella and pili but also by a less-understood process called gliding motility. During this process, rod-shaped bacteria move smoothly along their long axis without any visible morphological changes besides occasional bending. For this reason, the molecular mechanism of gliding motility and its origin have long remained a complete mystery. An important breakthrough in the understanding of gliding motility came from single cell and genetic studies in the delta-proteobacterium Myxococcus xanthus. These early studies revealed, for the first time, the existence of bacterial Focal Adhesion complexes (FA. FAs are formed at the bacterial pole and rapidly move towards the opposite cell pole. Their attachment to the underlying surface is linked to cell propulsion, in a process similar to the rearward translocation of actomyosin complexes in Apicomplexans. The protein machinery that forms at FAs was shown to contain up to seventeen proteins predicted to localize in all layers of the bacterial cell envelope, the cytosolic face, the inner membrane (IM, the periplasmic space and the outer membrane (OM. Among these proteins, a proton-gated channel at the inner membrane was identified as the molecular motor. Thus, thrust generation requires the transduction of traction forces generated at the inner membrane through the cell envelope beyond the rigid barrier of the bacterial peptidoglycan.

  14. Biomolecular Nano-Flow-Sensor to Measure Near-Surface Flow

    Directory of Open Access Journals (Sweden)

    Noji Hiroyuki

    2009-01-01

    Full Text Available Abstract We have proposed and experimentally demonstrated that the measurement of the near-surface flow at the interface between a liquid and solid using a 10 nm-sized biomolecular motor of F1-ATPase as a nano-flow-sensor. For this purpose, we developed a microfluidic test-bed chip to precisely control the liquid flow acting on the F1-ATPase. In order to visualize the rotation of F1-ATPase, several hundreds nanometer-sized particle was immobilized at the rotational axis of F1-ATPase to enhance the rotation to be detected by optical microscopy. The rotational motion of F1-ATPase, which was immobilized on an inner surface of the test-bed chip, was measured to obtain the correlation between the near-surface flow and the rotation speed of F1-ATPase. As a result, we obtained the relationship that the rotation speed of F1-ATPase was linearly decelerated with increasing flow velocity. The mechanism of the correlation between the rotation speed and the near-surface flow remains unclear, however the concept to use biomolecule as a nano-flow-sensor was proofed successfully. (See supplementary material 1 Electronic supplementary material The online version of this article (doi:10.1007/s11671-009-9479-3 contains supplementary material, which is available to authorized users. Click here for file

  15. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    interneurons and exert a direct (willful) muscle control with the aid of a context-dependent integration of somatosensory and visual information at cortical level. However, spinal networks also play an important role. Sensory feedback through spinal circuitries is integrated with central motor commands...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...... and contributes importantly to the muscle activity underlying voluntary movements. Regulation of spinal interneurons is used to switch between motor states such as locomotion (reciprocal innervation) and stance (coactivation pattern). Cortical regulation of presynaptic inhibition of sensory afferents may focus...

  16. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... properties of this facility in the path from synaptic sites to the motor axon is reviewed with emphasis on voltage sensitive ion channels and regulatory metabotropic transmitter pathways. The catalog of the intrinsic response properties, their underlying mechanisms, and regulation obtained from motoneurons...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  17. Movimento browniano e motores brownianos

    OpenAIRE

    Rezende, Guilherme Rocha de

    2012-01-01

    Neste trabalho utilizamos o formalismo da equação de Langevin generalizada, desenvolvido inicialmente por Robert Zwanzig e Hazime Mori, para estudarmos o comportamento de um tipo de motor browniano o motor liga-desliga aplicado no estudo de um separador de partículas e em um tipo de motor molecular: a cinesina. Neste estudo escolhemos quatro funções memórias diferentes e analisamos a influência destas memórias na velocidade e eficiência do motor browniano. ____________________________________...

  18. Self-Assembly Supramolecular Systems toward Molecular Machines and Motors%具有分子机器、分子开关功能的自组装超分子体系

    Institute of Scientific and Technical Information of China (English)

    陈慧兰

    2001-01-01

    Self-assembly, self-organization and self-replication, that are central to nature' s forms and functions, are now becoming feasible to construct large and intricate, yet highly ordered functioning molecular and supramolecular entities. This paper introduced the recently new progress for a kind of special rotaxane and catenane supramoculars having functions of molecular shuttle or molecular switch, as well as the chemical and biological systems toward molecular machines and motors.%本文介绍了具有分子梭或分子开关性质的新型轮烷和索烃超分子以及具有分子机器功能的其它类型化学和生物分子的国际研究最新动态。

  19. Molecular Motor MYO1C, Acetyltransferase KAT6B and Osteogenetic Transcription Factor RUNX2 Expression in Human Masseter Muscle Contributes to Development of Malocclusion

    Science.gov (United States)

    Desh, Heather; Gray, S Lauren; Horton, Michael J; Raoul, Gwenael; Rowlerson, Anthea M; Ferri, Joel; Vieira, Alexandre R; Sciote, James J

    2014-01-01

    Objective Type I myosins are molecular motors necessary for glucose transport in the cytoplasm and initiation of transcription in the nucleus. Two of these, MYO1H and MYO1C, are paralogs which may be important in the development of malocclusion. The objective of this study was to investigate their gene expression in the masseter muscle of malocclusion subjects. Two functionally related proteins known to contribute to malocclusion were also investigated: KAT6B (a chromatin remodeling epigenetic enzyme which is activated by MYO1C) and RUNX2 (a transcription factor regulating osteogenesis which is activated by KAT6B). Design Masseter muscle samples and malocclusion classifications were obtained from orthognathic surgery subjects. Muscle was sectioned and immunostained to determine fiber type properties. RNA was isolated from the remaining sample to determine expression levels for the four genes by TaqMan® RT-PCR. Fiber type properties, gene expression quantities and malocclusion classification were compared. Results There were very significant associations (P<0.0000001) between MYO1C and KAT6B expressions. There were also significant associations (P<0.005) between RUNX2 expression and masseter muscle type II fiber properties. Very few significant associations were identified between MYO1C and masseter muscle fiber type properties. Conclusions The relationship between MYO1C and KAT6B suggests that the two are interacting in chromatin remodeling for gene expression. This is the nuclear myosin1 (NM1) function of MYO1C. A surprising finding is the relationship between RUNX2 and type II masseter muscle fibers, since RUNX2 expression in mature muscle was previously unknown. Further investigations are necessary to elucidate the role of RUNX2 in adult masseter muscle. PMID:24698832

  20. Crystallographic and molecular dynamics analysis of loop motions unmasking the peptidoglycan-binding site in stator protein MotB of flagellar motor.

    Directory of Open Access Journals (Sweden)

    Cyril F Reboul

    Full Text Available BACKGROUND: The C-terminal domain of MotB (MotB-C shows high sequence similarity to outer membrane protein A and related peptidoglycan (PG-binding proteins. It is believed to anchor the power-generating MotA/MotB stator unit of the bacterial flagellar motor to the peptidoglycan layer of the cell wall. We previously reported the first crystal structure of this domain and made a puzzling observation that all conserved residues that are thought to be essential for PG recognition are buried and inaccessible in the crystal structure. In this study, we tested a hypothesis that peptidoglycan binding is preceded by, or accompanied by, some structural reorganization that exposes the key conserved residues. METHODOLOGY/PRINCIPAL FINDINGS: We determined the structure of a new crystalline form (Form B of Helicobacter pylori MotB-C. Comparisons with the existing Form A revealed conformational variations in the petal-like loops around the carbohydrate binding site near one end of the β-sheet. These variations are thought to reflect natural flexibility at this site required for insertion into the peptidoglycan mesh. In order to understand the nature of this flexibility we have performed molecular dynamics simulations of the MotB-C dimer. The results are consistent with the crystallographic data and provide evidence that the three loops move in a concerted fashion, exposing conserved MotB residues that have previously been implicated in binding of the peptide moiety of peptidoglycan. CONCLUSION/SIGNIFICANCE: Our structural analysis provides a new insight into the mechanism by which MotB inserts into the peptidoglycan mesh, thus anchoring the power-generating complex to the cell wall.

  1. An accessible hydrophobic surface is a key element of the molecular chaperone action of Atp11p.

    Science.gov (United States)

    Sheluho, D; Ackerman, S H

    2001-10-26

    Atp11p is a soluble protein of mitochondria that binds unassembled beta subunits of the F(1)-ATPase and prevents them from aggregating in the matrix. In this report, we show that Atp11p protects the insulin B chain from aggregating in vitro and therefore acts as a molecular chaperone. The chaperone action of Atp11p is mediated by hydrophobic interactions. An accessible hydrophobic surface in Atp11p was identified with the environment-sensitive fluorescent probe 1,1'-bis(4-anilino-5-napththalenesulfonic acid (bis-ANS). The spectral changes of bis-ANS in the presence of Atp11p indicate that the probe binds to a nonpolar region of the protein. Furthermore, the dye quenches the fluorescence of Atp11p tryptophan residues in a concentration-dependent manner. Although up to three molecules of bis-ANS can bind cooperatively to Atp11p, the binding of only one dye molecule is sufficient to virtually eliminate the chaperone activity of the protein.

  2. Motor syndromes.

    Science.gov (United States)

    Corea, Francesco; Micheli, Sara

    2012-01-01

    Motor disturbances alone or associated with other focal deficits are the most common symptoms suggesting a neurovascular event. An appropriate clinical assessment of these signs and symptoms may help physicians to better diagnose and to both better treat and predict outcome. In this paper the main clinical features of motor deficit are described together with other motor-related events such as ataxia and movement disturbances.

  3. Motor homopolar

    OpenAIRE

    Agustín Martín Muñoz

    2007-01-01

    Mostramos la construcción de un modelo de motor homopolar, uno de los más antiguos tipos de motores eléctricos. Se caracterizan porque el campo magnético del imán mantiene siempre la misma polaridad (de ahí su nombre, del griego homos, igual), de modo que, cuando una corriente eléctrica atraviesa el campo magnético, aparece una fuerza que hace girar los elementos no fijados mecánicamente. En el sencillísimo motor homopolar colgado (Schlichting y Ucke 2004), el imán puede girar ...

  4. Ultrasonic Motors

    Science.gov (United States)

    2003-06-01

    and T. Higuchi, "Cylindrical Micro Ultrasonic Motor Utilizing Bulk Lead Zirconate Titanate (PZT)," Japanese Journal of Applied Physics Part 1-Regular Papers Short Notes & Review Papers, vol. 38, pp. 3347-3350, 1999.

  5. An elastic-diffusion model for myosin VI molecular motor in a periodic potential field%肌球蛋白VI分子马达周期势场下的弹性扩散模型

    Institute of Scientific and Technical Information of China (English)

    李晨璞; 韩英荣; 展永; 胡金江; 张礼刚; 曲蛟

    2013-01-01

    Because of the special structure and intracellular functions of myosin VI molecular motor, its dynamic principle has become a research focus. Starting from its structure and experimental phenomenon, the elastic-diffusion model of myosin VI in a periodic potential field is established, and the stochastic dynamics of the molecular motors, which conform to the Langevin equation, is analyzed by Monte Carlo simulations. By means of the environmental noise, myosin VI molecular motors could take stable stepping motion and effective transport according to its elastic potential energy and periodic potential of track, and a load can weaken the transportation power of the molecular motor system. For a given elastic coefficient, the longer the elastic chain of myosin VI, the lower the average velocity of it. By selecting a reasonable size of elasticity coefficient, the average velocity can be the maximum for a given elastic chain. In addition, the load can increase exponentially the mean dwelling time of myosin VI at the connection site.%肌球蛋白VI分子马达因其特殊的结构及胞内功能,其动力学原理成为研究的热点。从肌球蛋白VI自身结构和实验现象出发,建立其弹性扩散模型,并通过Monte Carlo方法分析了肌球蛋白VI满足朗之万方程的随机动力学行为。结果表明,在环境噪声作用下,具有弹性势能和轨道周期势能的肌球蛋白VI可以进行梯跳运动和有效的输运,但负载力会减弱分子马达系统的输运能力;当弹性系数一定时,弹性链越长平均速度越小,当弹性链长度一定时,合理选择弹性系数平均速度可达到最大值;另外,负载力的存在使肌球蛋白VI在接触位点的平均驻留时间呈指数增加。

  6. Theory for strength and stability of an unusual "ligand-receptor" bond: a microtubule attached to a wall by molecular motor tethers

    CERN Document Server

    Ghanti, Dipanwita

    2016-01-01

    A microtubule (MT) is a tubular stiff filament formed by a hierarchical organization of tubulin proteins. We develop a stochastic kinetic model for studying the strength and stability of a pre-formed attachment of a MT with a rigid wall where the MT is tethered to the wall by a group of motor proteins. Such an attachment, formed by the specific interactions between the MT and the motors, is an analog of ligand-receptor bonds, the MT and the motors anchored on the wall being the counterparts of the ligand and receptors, respectively. However, unlike other ligands, the length of a MT can change with time because of its polymerization-depolymerization kinetics. The simple model developed here is motivated by the MTs linked to the cell cortex by dynein motors. We present the theory for both force-ramp and force-clamp conditions. In the force-ramp protocol we investigate the strength of the attachment by assuming imposition of a time-dependent external load tension that increases linearly with time till the attach...

  7. Motor Planning.

    Science.gov (United States)

    Wong, Aaron L; Haith, Adrian M; Krakauer, John W

    2015-08-01

    Motor planning colloquially refers to any process related to the preparation of a movement that occurs during the reaction time prior to movement onset. However, this broad definition encompasses processes that are not strictly motor-related, such as decision-making about the identity of task-relevant stimuli in the environment. Furthermore, the assumption that all motor-planning processes require processing time, and can therefore be studied behaviorally by measuring changes in the reaction time, needs to be reexamined. In this review, we take a critical look at the processes leading from perception to action and suggest a definition of motor planning that encompasses only those processes necessary for a movement to be executed-that is, processes that are strictly movement related. These processes resolve the ambiguity inherent in an abstract goal by defining a specific movement to achieve it. We propose that the majority of processes that meet this definition can be completed nearly instantaneously, which means that motor planning itself in fact consumes only a small fraction of the reaction time. © The Author(s) 2014.

  8. THE MOTOR

    DEFF Research Database (Denmark)

    Gammelgaard Nielsen, Anders

    2011-01-01

    MOTOR is the first assignment that students at Unit 1a of the School of Architecture are introduced to. The purpose of the assignment is to shake up the students and their preconceptions of what architec- ture is. This is done by introducing them to a working method that al- lows them to develop...

  9. THE MOTOR

    DEFF Research Database (Denmark)

    Gammelgaard Nielsen, Anders

    2011-01-01

    MOTOR is the first assignment that students at Unit 1a of the School of Architecture are introduced to. The purpose of the assignment is to shake up the students and their preconceptions of what architec- ture is. This is done by introducing them to a working method that al- lows them to develop...

  10. Locomotion of chemically powered autonomous nanowire motors

    Science.gov (United States)

    Wang, Lin; Li, Longqiu; Li, Tianlong; Zhang, Guangyu; Sun, Qian

    2015-08-01

    Physical insights on the hydrodynamics and locomotion of self-propelled nanowire motor under nonequilibrium steady state are investigated using finite element method in accordance with hybrid molecular dynamics/multiparticle collision dynamics and rigid body dynamics. Nanowire motor is discretized into finite segments, and forces of solvent molecule acting on the motor are assumed to be the sum of forces acting on all segments of the motor. We show that the locomotion of nanowire motor is mainly determined by the imbalance forces acting on the catalytic and noncatalytic segments. The average velocity along the axis increases significantly as a function of time prior to reaching equilibrium. The length of nanowire motor shows negligible effect on the velocity of the motor. Preliminary experimental results are provided to validate the current model.

  11. Functional and molecular plasticity of gamma and alpha-1 GABAA receptor subunits in the dorsal motor nucleus of the vagus after experimentally-induced diabetes.

    Science.gov (United States)

    Boychuk, Carie R; Smith, Katalin Cs; Smith, Bret N

    2017-08-23

    Chronic experimentally-induced hyperglycemia augments subunit specific gamma-aminobutyric acid A (GABAA) receptor-mediated inhibition of parasympathetic preganglionic motor neurons in the dorsal motor nucleus of the vagus (DMV). However, the contribution of α1 or γ GABAA receptor subunits, which are ubiquitously expressed on central nervous system neurons, to this elevation in inhibitory tone have not been determined. This study investigated the effect of chronic hyperglycemia/hypoinsulinemia on α1- and γ-subunit specific GABAA receptor-mediated inhibition using electrophysiological recordings in vitro and quantitative (q)RT-PCR. DMV neurons from streptozotocin-treated mice demonstrated enhancement of both phasic and tonic inhibitory currents in response to application of the α1-subunit selective GABAA receptor positive allosteric modulator, zolpidem. Responses to low concentrations of the GABAA receptor antagonist, gabazine suggested an additional increased contribution of γ-subunit-containing receptors to tonic currents in DMV neurons. Consistent with the functional elevation in α1- and γ-subunit-dependent activity, transcription of both the α1- and γ2-subunits was increased in the dorsal vagal complex of streptozotocin-treated mice. Overall these findings suggest an increased sensitivity to both zolpidem and gabazine after several days of hyperglycemia/hypoinsulinemia, which could contribute to altered parasympathetic output from DMV neurons in diabetes. Copyright © 2017, Journal of Neurophysiology.

  12. The Molecular Motor KIF1A Transports the TrkA Neurotrophin Receptor and Is Essential for Sensory Neuron Survival and Function.

    Science.gov (United States)

    Tanaka, Yosuke; Niwa, Shinsuke; Dong, Ming; Farkhondeh, Atena; Wang, Li; Zhou, Ruyun; Hirokawa, Nobutaka

    2016-06-15

    KIF1A is a major axonal transport motor protein, but its functional significance remains elusive. Here we show that KIF1A-haploinsufficient mice developed sensory neuropathy. We found progressive loss of TrkA(+) sensory neurons in Kif1a(+/-) dorsal root ganglia (DRGs). Moreover, axonal transport of TrkA was significantly disrupted in Kif1a(+/-) neurons. Live imaging and immunoprecipitation assays revealed that KIF1A bound to TrkA-containing vesicles through the adaptor GTP-Rab3, suggesting that TrkA is a cargo of the KIF1A motor. Physiological measurements revealed a weaker capsaicin response in Kif1a(+/-) DRG neurons. Moreover, these neurons were hyposensitive to nerve growth factor, which could explain the reduced neuronal survival and the functional deficiency of the pain receptor TRPV1. Because phosphatidylinositol 3-kinase (PI3K) signaling significantly rescued these phenotypes and also increased Kif1a mRNA, we propose that KIF1A is essential for the survival and function of sensory neurons because of the TrkA transport and its synergistic support of the NGF/TrkA/PI3K signaling pathway.

  13. Molecular hydrogen (H2) emissions and their isotopic signatures (H/D) from a motor vehicle : implications on atmospheric H2

    NARCIS (Netherlands)

    Vollmer, M.K.; Walter, S.; Bond, S.W.; Soltic, P.; Röckmann, T.

    2010-01-01

    Molecular hydrogen (H2), its isotopic signature (deuterium/hydrogen, δD), carbon monoxide (CO) and other compounds were studied in the exhaust of a passenger car engine fuelled with gasoline or methane and run under variable air-fuel ratios and operating modes. H2 and CO concentrations were largely

  14. Molecular hydrogen (H2) emissions and their isotopic signatures (H/D) from a motor vehicle : implications on atmospheric H2

    NARCIS (Netherlands)

    Vollmer, M.K.; Walter, S.; Bond, S.W.; Soltic, P.; Röckmann, T.

    2010-01-01

    Molecular hydrogen (H2), its isotopic signature (deuterium/hydrogen, δD), carbon monoxide (CO) and other compounds were studied in the exhaust of a passenger car engine fuelled with gasoline or methane and run under variable air-fuel ratios and operating modes. H2 and CO concentrations were largely

  15. Engineering molecular machines

    Science.gov (United States)

    Erman, Burak

    2016-04-01

    Biological molecular motors use chemical energy, mostly in the form of ATP hydrolysis, and convert it to mechanical energy. Correlated thermal fluctuations are essential for the function of a molecular machine and it is the hydrolysis of ATP that modifies the correlated fluctuations of the system. Correlations are consequences of the molecular architecture of the protein. The idea that synthetic molecular machines may be constructed by designing the proper molecular architecture is challenging. In their paper, Sarkar et al (2016 New J. Phys. 18 043006) propose a synthetic molecular motor based on the coarse grained elastic network model of proteins and show by numerical simulations that motor function is realized, ranging from deterministic to thermal, depending on temperature. This work opens up a new range of possibilities of molecular architecture based engine design.

  16. Motor neurons and the sense of place.

    Science.gov (United States)

    Jessell, Thomas M; Sürmeli, Gülşen; Kelly, John S

    2011-11-03

    Seventy years ago George Romanes began to document the anatomical organization of the spinal motor system, uncovering a multilayered topographic plan that links the clustering and settling position of motor neurons to the spatial arrangement and biomechanical features of limb muscles. To this day, these findings have provided a structural foundation for analysis of the neural control of movement and serve as a guide for studies to explore mechanisms that direct the wiring of spinal motor circuits. In this brief essay we outline the core of Romanes's findings and place them in the context of recent studies that begin to provide insight into molecular programs that assign motor pool position and to resolve how motor neuron position shapes circuit assembly. Romanes's findings reveal how and why neuronal positioning contributes to sensory-motor connectivity and may have relevance to circuit organization in other regions of the central nervous system. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Expression of NR2B in cerebellar granule cells specifically facilitates effect of motor training on motor learning.

    Science.gov (United States)

    Jiao, Jianwei; Nakajima, Akira; Janssen, William G M; Bindokas, Vytautas P; Xiong, Xiaoli; Morrison, John H; Brorson, James R; Tang, Ya-Ping

    2008-02-27

    It is believed that gene/environment interaction (GEI) plays a pivotal role in the development of motor skills, which are acquired via practicing or motor training. However, the underlying molecular/neuronal mechanisms are still unclear. Here, we reported that the expression of NR2B, a subunit of NMDA receptors, in cerebellar granule cells specifically enhanced the effect of voluntary motor training on motor learning in the mouse. Moreover, this effect was characterized as motor learning-specific and developmental stage-dependent, because neither emotional/spatial memory was affected nor was the enhanced motor learning observed when the motor training was conducted starting at the age of 3 months old in these transgenic mice. These results indicate that changes in the expression of gene(s) that are involved in regulating synaptic plasticity in cerebellar granule cells may constitute a molecular basis for the cerebellum to be involved in the GEI by facilitating motor skill learning.

  18. Expression of NR2B in cerebellar granule cells specifically facilitates effect of motor training on motor learning.

    Directory of Open Access Journals (Sweden)

    Jianwei Jiao

    Full Text Available It is believed that gene/environment interaction (GEI plays a pivotal role in the development of motor skills, which are acquired via practicing or motor training. However, the underlying molecular/neuronal mechanisms are still unclear. Here, we reported that the expression of NR2B, a subunit of NMDA receptors, in cerebellar granule cells specifically enhanced the effect of voluntary motor training on motor learning in the mouse. Moreover, this effect was characterized as motor learning-specific and developmental stage-dependent, because neither emotional/spatial memory was affected nor was the enhanced motor learning observed when the motor training was conducted starting at the age of 3 months old in these transgenic mice. These results indicate that changes in the expression of gene(s that are involved in regulating synaptic plasticity in cerebellar granule cells may constitute a molecular basis for the cerebellum to be involved in the GEI by facilitating motor skill learning.

  19. Gross motor control

    Science.gov (United States)

    Gross motor control is the ability to make large, general movements (such as waving an arm or lifting a leg). ... Gross motor control is a milestone in the development of an infant. Infants develop gross motor control before they develop ...

  20. Motor control for a brushless DC motor

    Science.gov (United States)

    Peterson, William J. (Inventor); Faulkner, Dennis T. (Inventor)

    1985-01-01

    This invention relates to a motor control system for a brushless DC motor having an inverter responsively coupled to the motor control system and in power transmitting relationship to the motor. The motor control system includes a motor rotor speed detecting unit that provides a pulsed waveform signal proportional to rotor speed. This pulsed waveform signal is delivered to the inverter to thereby cause an inverter fundamental current waveform output to the motor to be switched at a rate proportional to said rotor speed. In addition, the fundamental current waveform is also pulse width modulated at a rate proportional to the rotor speed. A fundamental current waveform phase advance circuit is controllingly coupled to the inverter. The phase advance circuit is coupled to receive the pulsed waveform signal from the motor rotor speed detecting unit and phase advance the pulsed waveform signal as a predetermined function of motor speed to thereby cause the fundamental current waveform to be advanced and thereby compensate for fundamental current waveform lag due to motor winding reactance which allows the motor to operate at higher speeds than the motor is rated while providing optimal torque and therefore increased efficiency.

  1. High efficiency motors; Motores de alta eficiencia

    Energy Technology Data Exchange (ETDEWEB)

    Uranga Favela, Ivan Jaime [Energia Controlada de Mexico, S. A. de C. V., Mexico, D. F. (Mexico)

    1992-12-31

    This paper is a technical-financial study of the high efficiency and super-premium motors. As it is widely known, more than 60% of the electrical energy generated in the country is used for the operation of motors, in industry as well as in commerce. Therefore the importance that the motors have in the efficient energy use. [Espanol] El presente trabajo es un estudio tecnico-financiero de los motores de alta eficiencia y los motores super premium. Como es ampliamente conocido, mas del 60% de la energia electrica generada en el pais, es utilizada para accionar motores, dentro de la industria y el comercio. De alli la importancia que los motores tienen en el uso eficiente de la energia.

  2. Motor Priming in Neurorehabilitation

    OpenAIRE

    Stoykov, Mary Ellen; Madhavan, Sangeetha

    2015-01-01

    Priming is a type of implicit learning wherein a stimulus prompts a change in behavior. Priming has been long studied in the field of psychology. More recently, rehabilitation researchers have studied motor priming as a possible way to facilitate motor learning. For example, priming of the motor cortex is associated with changes in neuroplasticity that are associated with improvements in motor performance. Of the numerous motor priming paradigms under investigation, only a few ...

  3. Motor Priming in Neurorehabilitation

    OpenAIRE

    Stoykov, Mary Ellen; Madhavan, Sangeetha

    2015-01-01

    Priming is a type of implicit learning wherein a stimulus prompts a change in behavior. Priming has been long studied in the field of psychology. More recently, rehabilitation researchers have studied motor priming as a possible way to facilitate motor learning. For example, priming of the motor cortex is associated with changes in neuroplasticity that are associated with improvements in motor performance. Of the numerous motor priming paradigms under investigation, only a few ...

  4. Motor neuropathies and lower motor neuron syndromes.

    Science.gov (United States)

    Verschueren, A

    2017-05-01

    Motor or motor-predominant neuropathies may arise from disease processes affecting the motor axon and/or its surrounding myelin. Lower motor neuron syndrome (LMNS) arises from a disease process affecting the spinal motor neuron itself. The term LMNS is more generally used, rather than motor neuronopathy, although both entities are clinically similar. Common features are muscle weakness (distal or proximal) with atrophy and hyporeflexia, but no sensory involvement. They can be acquired or hereditary. Immune-mediated neuropathies (multifocal motor neuropathy, motor-predominant chronic inflammatory demyelinating polyneuropathy) are important to identify, as effective treatments are available. Other acquired neuropathies, such as infectious, paraneoplastic and radiation-induced neuropathies are also well known. Focal LMNS is an amyotrophic lateral sclerosis (ALS)-mimicking syndrome especially affecting young adults. The main hereditary LMNSs in adulthood are Kennedy's disease, late-onset spinal muscular atrophy and distal hereditary motor neuropathies. Motor neuropathies and LMNS are all clinical entities that should be better known, despite being rare diseases. They can sometimes be difficult to differentially diagnose from other diseases, particularly from the more frequent ALS in its pure LMN form. Nevertheless, correct identification of these syndromes is important because their treatment and prognoses are definitely different. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Molecular hydrogen (H2 emissions and their isotopic signatures (H/D from a motor vehicle: implications on atmospheric H2

    Directory of Open Access Journals (Sweden)

    T. Röckmann

    2010-06-01

    Full Text Available Molecular hydrogen (H2, its isotopic signature (deuterium/hydrogen, δD, carbon monoxide (CO, and other compounds were studied in the exhaust of a passenger car engine fuelled with gasoline or methane and run under variable air-fuel ratios and operating modes. H2 and CO concentrations were largely reduced downstream of the three-way catalytic converter (TWC compared to levels upstream, and showed a strong dependence on the air-fuel ratio (expressed as lambda, λ. The isotopic composition of H2 ranged from δD = −140‰ to δD = −195‰ upstream of the TWC but these values decreased to −270‰ to −370‰ after passing through the TWC. Post-TWC δD values for the fuel-rich range showed a strong dependence on TWC temperature with more negative δD for lower temperatures. These effects are attributed to a rapid temperature-dependent H-D isotope equilibration between H2 and water (H2O. In addition, post TWC δD in H2 showed a strong dependence on the fraction of removed H2, suggesting isotopic enrichment during catalytic removal of H2 with enrichment factors (ε ranging from −39.8‰ to −15.5‰ depending on the operating mode. Our results imply that there may be considerable variability in real-world δD emissions from vehicle exhaust, which may mainly depend on TWC technology and exhaust temperature regime. This variability is suggestive of a δD from traffic that varies over time, by season, and by geographical location. An earlier-derived integrated pure (end-member δD from anthropogenic activities of −270‰ (Rahn et al., 2002 can be explained as a mixture of mainly vehicle emissions from cold starts and fully functional TWCs, but enhanced δD values by >50‰ are likely for regions where TWC technology is not fully implemented. Our results also suggest that a full hydrogen isotope analysis on fuel and exhaust gas may greatly aid at understanding process-level reactions in the exhaust gas, in particular in the TWC.

  6. Molecular hydrogen (H2 emissions and their isotopic signatures (H/D from a motor vehicle: implications on atmospheric H2

    Directory of Open Access Journals (Sweden)

    T. Röckmann

    2010-02-01

    Full Text Available Molecular hydrogen (H2, its isotopic signature (deuterium/hydrogen, δD, carbon monoxide (CO and other compounds were studied in the exhaust of a passenger car engine fuelled with gasoline or methane and run under variable air-fuel ratios and operating modes. H2 and CO concentrations were largely reduced downstream of the three-way catalytic converter (TWC compared to levels upstream, and showed a strong dependence on the air-fuel ratio (expressed as lambda, λ. The isotopic composition of H2 ranged from δD=–140‰ to δD=–195‰ upstream of the TWC but these values decreased to –270‰ to –370‰ after passing through the TWC. Post-TWC δD values for the fuel-rich range showed a strong dependence on TWC temperature with more negative δD for lower temperatures. These effects are attributed to a rapid temperature-dependent H-D isotope equilibration between H2 and water (H2O. In addition, post TWC δD in H2 showed a strong dependence on the fraction of removed H2, suggesting isotopic enrichment during catalytic removal of H2 with enrichment factors (ε ranging from –39.8‰ to –15.5‰ depending on the operating mode. Our results imply that there may be considerable variability in real-world δD emissions from vehicle exhaust, which may mainly depend on TWC technology and exhaust temperature regime. This variability is suggestive of a δD from traffic that varies over time, by season, and by geographical location. An earlier-derived integrated pure (end-member δD from anthropogenic activities of –270‰ (Rahn et al., 2002 can be explained as a mixture of mainly vehicle emissions from cold starts and fully functional TWCs, but enhanced δD values by >50‰ are likely for regions where TWC technology is not fully implemented. Our results also suggest that a full hydrogen isotope analysis on fuel and exhaust gas may greatly aid at understanding process-level reactions in the exhaust gas, in particular in the TWC.

  7. Crosstalk between non-processive myosin motors mediated by the actin filament elasticity

    OpenAIRE

    2011-01-01

    Many biological processes involve the action of molecular motors that interact with the cell cytoskeleton. Some processes, such as the transport of cargoes is achieved mainly by the action of individual motors. Other, such as cell motility and division, require the cooperative work of many motors. Collective motor dynamics can be quite complex and unexpected. One beautiful example is the bidirectional ("back and forth") motion of filaments which is induced when the motors within a group exert...

  8. Electric motor handbook

    CERN Document Server

    Chalmers, B J

    2013-01-01

    Electric Motor Handbook aims to give practical knowledge in a wide range of capacities such as plant design, equipment specification, commissioning, operation and maintenance. The book covers topics such as the modeling of steady-state motor performance; polyphase induction, synchronous, and a.c. commutator motors; ambient conditions, enclosures, cooling and loss dissipation; and electrical supply systems and motor drives. Also covered are topics such as variable-speed drives and motor control; materials and motor components; insulation types, systems, and techniques; and the installation, sit

  9. Architecture and mechanism of the central gear in an ancient molecular timer.

    Science.gov (United States)

    Egli, Martin

    2017-03-01

    ferret out mechanistic aspects of the ATPase, auto-phosphorylation and auto-dephosphorylation reactions catalysed by the homo-hexamer. Comparisons between the structure of KaiC and those of nanomachines such as F1-ATPase and CaMKII also exposed shared architectural features (KaiC/ATPase), mechanistic principles (KaiC/CaMKII) and phenomena, such as subunit exchange between hexameric particles critical for function (clock synchronization, KaiABC; memory-storage, CaMKII). © 2017 The Author(s).

  10. Molecular Stirrers in Action

    NARCIS (Netherlands)

    Chen, Jiawen; Kistemaker, Jos C. M.; Robertus, Jort; Feringa, Ben L.

    2014-01-01

    A series of first-generation light-driven molecular motors with rigid substituents of varying length was synthesized to act as "molecular stirrers". Their rotary motion was studied by H-1 NMR and UV-vis absorption spectroscopy in a variety of solvents with different polarity and viscosity. Quantitat

  11. Disulfide bond formation between the COOH-terminal domain of the beta subunits and the gamma and epsilon subunits of the Escherichia coli F1-ATPase. Structural implications and functional consequences.

    Science.gov (United States)

    Aggeler, R; Haughton, M A; Capaldi, R A

    1995-04-21

    A set of mutants of the Escherichia coli F1F0-type ATPase has been generated by site-directed mutagenesis as follows: beta E381C, beta S383C, beta E381C/epsilon S108C, and beta S383C/epsilon S108C. Treatment of ECF1 isolated from any of these mutants with CuCl2 induces disulfide bond formation. For the single mutants, beta E381C and beta S383C, a disulfide bond is formed in essentially 100% yield between a beta subunit and the gamma subunit, probably at Cys87 based on the recent structure determination of F1 (Abrahams, J. P., Leslie, A. G. W., Lutter, R., and Walker, J. E. (1994) Nature 370, 621-628). In the double mutants, two disulfide bonds are formed, again in essentially full yield, one between beta and gamma, the other between a beta and the epsilon subunit via Cys108. The same two cross-links are produced with CuCl2 treatment of ECF1F0 isolated from either of the double mutants. These results show that the parts of gamma around residue 87 (a short alpha-helix) and the epsilon subunit interact with different beta subunits. The yield of covalent linkage of beta to gamma is nucleotide dependent and highest in ATP and much lower with ADP in catalytic sites. The yield of covalent linkage of beta to epsilon is also nucleotide dependent but in this case is highest in ADP and much lower in ATP. Disulfide bond formation between either beta and gamma, or beta and epsilon inhibits the ATPase activity of the enzyme in proportion to the yield of the cross-linked product. Chemical modification of the Cys at either position 381 or 383 of the beta subunit inhibits ATPase activity in a manner that appears to be dependent on the size of the modifying reagent. These results are as expected if movements of the catalytic site-containing beta subunits relative to the gamma and epsilon subunits are an essential part of the cooperativity of the enzyme.

  12. Introduction to ultrasonic motors

    Energy Technology Data Exchange (ETDEWEB)

    Sashida, Toshiiku; Kenjo, Takashi.

    1993-01-01

    The ultrasonic motor, invented in 1980, utilizes the piezoelectric effect in the ultrasonic frequency range to provide the motive force. (In conventional electric motors the motive force is electromagnetic.) The result is a motor with unusually good low-speed high-torque and power-to-weight characteristics. It has already found applications in camera autofocus mechanisms, medical equipment subject to high magnetic fields, and motorized car accessories. Its applications will increase as designers become more familiar with its unique characteristics. This book is the result of a collaboration between the inventor and an expert in conventional electric motors: the result is an introduction to the general theory presented in a way that links it to conventional motor theory. It will be invaluable both to motor designers and to those who design with and use electric motors as an introduction to this important new invention.

  13. Chronic motor tic disorder

    Science.gov (United States)

    Chronic vocal tic disorder; Tic - chronic motor tic disorder ... Chronic motor tic disorder is more common than Tourette syndrome . Chronic tics may be forms of Tourette syndrome. Tics usually start ...

  14. Piezoelectric Motors, an Overview

    OpenAIRE

    Karl Spanner; Burhanettin Koc

    2016-01-01

    Piezoelectric motors are used in many industrial and commercial applications. Various piezoelectric motors are available in the market. All of the piezoelectric motors use the inverse piezoelectric effect, where microscopically small oscillatory motions are converted into continuous or stepping rotary or linear motions. Methods of obtaining long moving distance have various drive and functional principles that make these motors categorized into three groups: resonance-drive (piezoelectric ult...

  15. Sliding of microtubules by a team of dynein motors: Understanding the effect of spatial distribution of motor tails and mutual exclusion of motor heads on microtubules

    Science.gov (United States)

    Singh, Hanumant Pratap; Takshak, Anjneya; Mall, Utkarsh; Kunwar, Ambarish

    2016-06-01

    Molecular motors are natural nanomachines that use the free energy released from ATP hydrolysis to generate mechanical forces. Cytoplasmic dynein motors often work collectively as a team to drive important processes such as axonal growth, proplatelet formation and mitosis, as forces generated by single motors are insufficient. A large team of dynein motors is used to slide cytoskeletal microtubules with respect to one another during the process of proplatelet formation and axonal growth. These motors attach to a cargo microtubule via their tail domains, undergo the process of detachment and reattachment of their head domains on another track microtubule, while sliding the cargo microtubule along the track. Traditional continuum/mean-field approaches used in the past are not ideal for studying the sliding mechanism of microtubules, as they ignore spatial and temporal fluctuations due to different possible distributions of motor tails on cargo filament, as well as binding/unbinding of motors from their track. Therefore, these models cannot be used to address important questions such as how the distribution of motor tails on microtubules, or how the mutual exclusion of motor heads on microtubule tracks affects the sliding velocity of cargo microtubule. To answer these, here we use a computational stochastic model where we model each dynein motor explicitly. In our model, we use both random as well as uniform distributions of dynein motors on cargo microtubule, as well as mutual exclusion of motors on microtubule tracks. We find that sliding velocities are least affected by the distribution of motor tails on microtubules, whereas they are greatly affected by mutual exclusion of motor heads on microtubule tracks. We also find that sliding velocity depends on the length of cargo microtubule if mutual exclusion among motor heads is considered.

  16. Electric Motor Thermal Management

    Energy Technology Data Exchange (ETDEWEB)

    Bennion, Kevin S [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-01

    Thermal management enables more efficient and cost-effective motors. This Annual Merit Review presentation describes the technical accomplishments and progress in electric motor thermal management R&D over the last year. This project supports a broad industry demand for data, analysis methods, and experimental techniques to improve and better understand motor thermal management.

  17. Fine tuning of molecular rotor function in photochemical molecular switches

    NARCIS (Netherlands)

    ter Wiel, Matthijs K. J.; Feringa, Ben L.

    2009-01-01

    Molecular switches are used as scaffolds for the construction of controlled molecular rotors. The internal position of the switching entity in the molecule controls the dynamic behaviour of the rotor moiety in the molecule. Six new molecular motors with o-xylyl rotor moieties were prepared on the ba

  18. A Reconfigurable Stepping Motor

    Science.gov (United States)

    Rogers, Charles; Selvaggi, Richard

    2009-04-01

    Multiphase brushless actuators, commonly known as the stepper motors, are ubiquitous for many precision control applications. Developments in the microelectronics have lead to their use as efficient drive motors for modern electric vehicles. Understanding the physics and the control logic for interfacing these transducers continues to be important for scientists and engineers. An overview of the stepping motor principles and interfacing requirements is presented and a simple working model used to teach the concepts of stepper motors is described and demonstrated. This model was used to design a much larger stepper motor required to precisely rotate a massive optical system in the undergraduate advanced physics laboratory.

  19. Induction motor control design

    CERN Document Server

    Marino, Riccardo; Verrelli, Cristiano M

    2010-01-01

    ""Nonlinear and Adaptive Control Design for Induction Motors"" is a unified exposition of the most important steps and concerns in the design of estimation and control algorithms for induction motors. A single notation and modern nonlinear control terminology is used to make the book accessible to readers who are not experts in electric motors at the same time as giving a more theoretical control viewpoint to those who are. In order to increase readability, the book concentrates on the induction motor, eschewing the much more complex and less-well-understood control of asynchronous motors. The

  20. Solid propellant motor

    Science.gov (United States)

    Shafer, J. I.; Marsh, H. E., Jr. (Inventor)

    1978-01-01

    A case bonded end burning solid propellant rocket motor is described. A propellant with sufficiently low modulus to avoid chamber buckling on cooling from cure and sufficiently high elongation to sustain the stresses induced without cracking is used. The propellant is zone cured within the motor case at high pressures equal to or approaching the pressure at which the motor will operate during combustion. A solid propellant motor with a burning time long enough that its spacecraft would be limited to a maximum acceleration of less than 1 g is provided by one version of the case bonded end burning solid propellant motor of the invention.

  1. Motor/generator

    Science.gov (United States)

    Hickam, Christopher Dale

    2008-05-13

    A motor/generator is provided for connecting between a transmission input shaft and an output shaft of a prime mover. The motor/generator may include a motor/generator housing, a stator mounted to the motor/generator housing, a rotor mounted at least partially within the motor/generator housing and rotatable about a rotor rotation axis, and a transmission-shaft coupler drivingly coupled to the rotor. The transmission-shaft coupler may include a clamp, which may include a base attached to the rotor and a plurality of adjustable jaws.

  2. Motor degradation prediction methods

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, J.R.; Kelly, J.F.; Delzingaro, M.J.

    1996-12-01

    Motor Operated Valve (MOV) squirrel cage AC motor rotors are susceptible to degradation under certain conditions. Premature failure can result due to high humidity/temperature environments, high running load conditions, extended periods at locked rotor conditions (i.e. > 15 seconds) or exceeding the motor`s duty cycle by frequent starts or multiple valve stroking. Exposure to high heat and moisture due to packing leaks, pressure seal ring leakage or other causes can significantly accelerate the degradation. ComEd and Liberty Technologies have worked together to provide and validate a non-intrusive method using motor power diagnostics to evaluate MOV rotor condition and predict failure. These techniques have provided a quick, low radiation dose method to evaluate inaccessible motors, identify degradation and allow scheduled replacement of motors prior to catastrophic failures.

  3. Neuroplasticity & Motor Learning

    DEFF Research Database (Denmark)

    Jensen, Jesper Lundbye

    Practice of a new motor task is usually associated with an improvement in performance. Indeed, if we stop practicing and return the next day to the same task, we find that our performance has been maintained and may even be better than it was at the start of the first day. This improvement...... is a measure of our ability to form and store a motor memory of the task. However, the initial memory of the task is labile and may be subject to interference. During and following motor learning plastic changes occur within the central nervous system. On one hand these changes are driven by motor practice......, on the other hand the changes underlie the formation of motor memory and the retention of improved motor performance. During motor learning changes may occur at many different levels within the central nervous system dependent on the type of task and training. Here, we demonstrate different studies from our...

  4. Piezoelectric Motors, an Overview

    Directory of Open Access Journals (Sweden)

    Karl Spanner

    2016-02-01

    Full Text Available Piezoelectric motors are used in many industrial and commercial applications. Various piezoelectric motors are available in the market. All of the piezoelectric motors use the inverse piezoelectric effect, where microscopically small oscillatory motions are converted into continuous or stepping rotary or linear motions. Methods of obtaining long moving distance have various drive and functional principles that make these motors categorized into three groups: resonance-drive (piezoelectric ultrasonic motors, inertia-drive, and piezo-walk-drive. In this review, a comprehensive summary of piezoelectric motors, with their classification from initial idea to recent progress, is presented. This review also includes some of the industrial and commercial applications of piezoelectric motors that are presently available in the market as actuators.

  5. Underediting of GluR2 mRNA, a neuronal death inducing molecular change in sporadic ALS, does not occur in motor neurons in ALS1 or SBMA.

    Science.gov (United States)

    Kawahara, Yukio; Sun, Hui; Ito, Kyoko; Hideyama, Takuto; Aoki, Masashi; Sobue, Gen; Tsuji, Shoji; Kwak, Shin

    2006-01-01

    Deficient RNA editing of the AMPA receptor subunit GluR2 at the Q/R site is a primary cause of neuronal death and recently has been reported to be a tightly linked etiological cause of motor neuron death in sporadic amyotrophic lateral sclerosis (ALS). We quantified the RNA editing efficiency of the GluR2 Q/R site in single motor neurons of rats transgenic for mutant human Cu/Zn-superoxide dismutase (SOD1) as well as patients with spinal and bulbar muscular atrophy (SBMA), and found that GluR2 mRNA was completely edited in all the motor neurons examined. It seems likely that the death cascade is different among the dying motor neurons in sporadic ALS, familial ALS with mutant SOD1 and SBMA.

  6. Dynamics and Thermodynamics of Molecular Machines

    DEFF Research Database (Denmark)

    Golubeva, Natalia

    2014-01-01

    Molecular machines, or molecular motors, are small biophysical devices that perform a variety of essential metabolic processes such as DNA replication, protein synthesis and intracellular transport. Typically, these machines operate by converting chemical energy into motion and mechanical work. Due...... to their microscopic size, molecular motors are governed by principles fundamentally different from those describing the operation of man-made motors such as car engines. In this dissertation the dynamic and thermodynamic properties of molecular machines are studied using the tools of nonequilibrium statistical...... of the important trade-off between power output and efficiency. Steric motor-motor interactions are shown to play an important thermodynamic role by enhancing the EMP as compared to the noninteracting case. Remarkably, the enhancement occurs at biologically relevant parameters. Finally, a generic model of motor...

  7. Bidirectionality From Cargo Thermal Fluctuations in Motor-Mediated Transport

    CERN Document Server

    Miles, Christopher E

    2016-01-01

    Molecular motor proteins serve as an essential component of intracellular transport by generating forces to haul cargoes along cytoskeletal filaments. In some circumstances, two species of motors that are directed oppositely (e.g. kinesin, dynein) can be attached to the same cargo. The resulting net motion is known to be bidirectional, but the mechanism of switching remains unclear. In this work, we propose a mean-field mathematical model of the mechanical interactions of two populations of molecular motors with diffusion of the cargo (thermal fluctuations) as the fundamental noise source. By studying a simplified model, the delayed response of motors to rapid fluctuations in the cargo is quantified, allowing for the reduction of the full model to two "characteristic positions" of each of the motor populations. The system is then found to be "metastable", switching between two distinct directional transport states, or bidirectional motion. The time to switch between these states is then investigated using WKB...

  8. Modularity for Motor Control and Motor Learning.

    Science.gov (United States)

    d'Avella, Andrea

    2016-01-01

    How the central nervous system (CNS) overcomes the complexity of multi-joint and multi-muscle control and how it acquires or adapts motor skills are fundamental and open questions in neuroscience. A modular architecture may simplify control by embedding features of both the dynamic behavior of the musculoskeletal system and of the task into a small number of modules and by directly mapping task goals into module combination parameters. Several studies of the electromyographic (EMG) activity recorded from many muscles during the performance of different tasks have shown that motor commands are generated by the combination of a small number of muscle synergies, coordinated recruitment of groups of muscles with specific amplitude balances or activation waveforms, thus supporting a modular organization of motor control. Modularity may also help understanding motor learning. In a modular architecture, acquisition of a new motor skill or adaptation of an existing skill after a perturbation may occur at the level of modules or at the level of module combinations. As learning or adapting an existing skill through recombination of modules is likely faster than learning or adapting a skill by acquiring new modules, compatibility with the modules predicts learning difficulty. A recent study in which human subjects used myoelectric control to move a mass in a virtual environment has tested this prediction. By altering the mapping between recorded muscle activity and simulated force applied on the mass, as in a complex surgical rearrangement of the tendons, it has been possible to show that it is easier to adapt to a perturbation that is compatible with the muscle synergies used to generate hand force than to a similar but incompatible perturbation. This result provides direct support for a modular organization of motor control and motor learning.

  9. A Cell Lysis and Protein Purification - Single Molecule Assay Devices for Evaluation of Genetically Engineered Proteins

    Science.gov (United States)

    Nakyama, Tetsuya; Tabata, Kazuhito; Noji, Hiroyuki; Yokokawa, Ryuji

    We have developed two devices applicable to evaluate genetically engineered proteins in single molecule assay: on-chip cell lysis device, and protein purification - assay device. A motor protein, F1-ATPase expressed in E.coli, was focused in this report as a target protein. Cell lysis was simply performed by applying pulse voltage between Au electrodes patterned by photolithography, and its efficiency was determined by absorptiometry. The subsequent processes, purification and assay of extracted proteins, were demonstrated in order to detect F1-ATPase and to evaluate its activity. The specific bonding between his-tag in F1-ATPase and Ni-NTA coated on a glass surface was utilized for the purification process. After immobilization of F1-ATPase, avidin-coated microspheres and adenosine tri-phosphate (ATP) solution were infused sequentially to assay the protein. Microsphere rotation was realized by activity of F1-ATPase corresponding to ATP hydrolysis. Results show that the cell lysis device, at the optimum condition, extracts enough amount of protein for single molecule assay. Once cell lysate was injected to the purification - assay device, proteins were diffused in the lateral direction in a Y-shape microchannel. The gradient of protein concentratioin provides an optimal concentration for the assay i.e. the highest density of rotating beads. Density of rotating beads is also affected by the initial concentration of protein injected to the device. The optimum concentration was achieved by our cell lysis device not by the conventional method by ultrasonic wave. Rotation speed was analyzed for several microspheres assayed in the purification - assay device, and the results were compatible to that of conventional assay in which F1-ATPase was purified in bulk scale. In conclusion, we have demonstrated on-chip cell lysis and assay appropriate for the sequential analysis without any pretreatment. On-chip devices replacing conventional bioanalytical methods will be

  10. ELECTRIC MOTOR CARS.

    Science.gov (United States)

    PASSENGER VEHICLES , ELECTRIC MOTORS), FEASIBILITY STUDIES, BATTERY COMPONENTS, ELECTRIC BATTERIES, FUEL CELLS, ENERGY CONVERSION, NUCLEAR ENERGY, THERMIONIC CONVERTERS , THERMOELECTRICITY, POWER EQUIPMENT, COSTS

  11. Roles of the orexin system in central motor control.

    Science.gov (United States)

    Hu, Bo; Yang, Nian; Qiao, Qi-Cheng; Hu, Zhi-An; Zhang, Jun

    2015-02-01

    The neuropeptides orexin-A and orexin-B are produced by one group of neurons located in the lateral hypothalamic/perifornical area. However, the orexins are widely released in entire brain including various central motor control structures. Especially, the loss of orexins has been demonstrated to associate with several motor deficits. Here, we first summarize the present knowledge that describes the anatomical and morphological connections between the orexin system and various central motor control structures. In the next section, the direct influence of orexins on related central motor control structures is reviewed at molecular, cellular, circuitry, and motor activity levels. After the summarization, the characteristic and functional relevance of the orexin system's direct influence on central motor control function are demonstrated and discussed. We also propose a hypothesis as to how the orexin system orchestrates central motor control in a homeostatic regulation manner. Besides, the importance of the orexin system's phasic modulation on related central motor control structures is highlighted in this regulation manner. Finally, a scheme combining the homeostatic regulation of orexin system on central motor control and its effects on other brain functions is presented to discuss the role of orexin system beyond the pure motor activity level, but at the complex behavioral level.

  12. Modeling Induction Motor Imbalances

    DEFF Research Database (Denmark)

    Armah, Kabenla; Jouffroy, Jerome; Duggen, Lars

    2016-01-01

    This paper gives a study into the development of a generalized model for a three-phase induction motor that offers flexibility of simulating balanced and unbalanced parameter scenarios. By analyzing the interaction of forces within the motor, we achieve our main objective of deriving the system...

  13. To What Extent Can Motor Imagery Replace Motor Execution While Learning a Fine Motor Skill?

    NARCIS (Netherlands)

    Sobierajewicz, Jagna; Szarkiewicz, Sylwia; Prekoracka-Krawczyk, Anna; Jaskowski, Wojciech; van der Lubbe, Robert Henricus Johannes

    2016-01-01

    Motor imagery is generally thought to share common mechanisms with motor execution. In the present study, we examined to what extent learning a fine motor skill by motor imagery may substitute physical practice. Learning effects were assessed by manipulating the proportion of motor execution and

  14. Induction motor control

    Science.gov (United States)

    Hansen, Irving G.

    Electromechanical actuators developed to date have commonly ultilized permanent magnet (PM) synchronous motors. More recently switched reluctance (SR) motors have been advocated due to their robust characteristics. Implications of work which utilized induction motors and advanced control techniques are discussed. When induction motors are operated from an energy source capable of controlling voltages and frequencies independently, drive characteristics are obtained which are superior to either PM or SR motors. By synthesizing the machine frequency from a high-frequency carrier (nominally 20 kHz), high efficiencies, low distortion, and rapid torque response are available. At this time multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of aerospace actuators. This effort is based upon high-frequency power distribution and management techniques developed by NASA for Space Station Freedom.

  15. Induction motor control

    Science.gov (United States)

    Hansen, Irving G.

    1990-01-01

    Electromechanical actuators developed to date have commonly ultilized permanent magnet (PM) synchronous motors. More recently switched reluctance (SR) motors have been advocated due to their robust characteristics. Implications of work which utilized induction motors and advanced control techniques are discussed. When induction motors are operated from an energy source capable of controlling voltages and frequencies independently, drive characteristics are obtained which are superior to either PM or SR motors. By synthesizing the machine frequency from a high-frequency carrier (nominally 20 kHz), high efficiencies, low distortion, and rapid torque response are available. At this time multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of aerospace actuators. This effort is based upon high-frequency power distribution and management techniques developed by NASA for Space Station Freedom.

  16. MISR Motor Data V003

    Data.gov (United States)

    National Aeronautics and Space Administration — This file contains the output for the Level 1A Motor data (Suggested Usage: MISR SCF processing needs the MISR motor data samples for the analysis of motor anomalies...

  17. Molecular machines open cell membranes

    Science.gov (United States)

    García-López, Víctor; Chen, Fang; Nilewski, Lizanne G.; Duret, Guillaume; Aliyan, Amir; Kolomeisky, Anatoly B.; Robinson, Jacob T.; Wang, Gufeng; Pal, Robert; Tour, James M.

    2017-08-01

    Beyond the more common chemical delivery strategies, several physical techniques are used to open the lipid bilayers of cellular membranes. These include using electric and magnetic fields, temperature, ultrasound or light to introduce compounds into cells, to release molecular species from cells or to selectively induce programmed cell death (apoptosis) or uncontrolled cell death (necrosis). More recently, molecular motors and switches that can change their conformation in a controlled manner in response to external stimuli have been used to produce mechanical actions on tissue for biomedical applications. Here we show that molecular machines can drill through cellular bilayers using their molecular-scale actuation, specifically nanomechanical action. Upon physical adsorption of the molecular motors onto lipid bilayers and subsequent activation of the motors using ultraviolet light, holes are drilled in the cell membranes. We designed molecular motors and complementary experimental protocols that use nanomechanical action to induce the diffusion of chemical species out of synthetic vesicles, to enhance the diffusion of traceable molecular machines into and within live cells, to induce necrosis and to introduce chemical species into live cells. We also show that, by using molecular machines that bear short peptide addends, nanomechanical action can selectively target specific cell-surface recognition sites. Beyond the in vitro applications demonstrated here, we expect that molecular machines could also be used in vivo, especially as their design progresses to allow two-photon, near-infrared and radio-frequency activation.

  18. Modelling of a DNA packaging motor

    Institute of Scientific and Technical Information of China (English)

    Qian Jun; Xie Ping; Xue Xiao-Guang; Wang Peng-Ye

    2009-01-01

    During the assembly of many viruses, a powerful molecular motor packages the genome into a preassembled capsid. The Bacillus subtilis phage φ29 is an excellent model system to investigate the DNA packaging mechanism because of its highly efficient in vitro DNA packaging activity and the development of a single-molecule packaging assay. Here we make use of structural and biochemical experimental data to build a physical model of DNA packaging by the φ29 DNA packaging motor. Based on the model, various dynamic behaviours such as the packaging rate, pause frequency and slip frequency under different ATP concentrations, ADP concentrations, external loads as well as capsid fillings are studied by using Monte Carlo simulation. Good agreement is obtained between the simulated and available experimental results. Moreover, we make testable predictions that should guide future experiments related to motor function.

  19. Elasticity, friction, and pathway of γ-subunit rotation in FoF1-ATP synthase.

    Science.gov (United States)

    Okazaki, Kei-ichi; Hummer, Gerhard

    2015-08-25

    We combine molecular simulations and mechanical modeling to explore the mechanism of energy conversion in the coupled rotary motors of FoF1-ATP synthase. A torsional viscoelastic model with frictional dissipation quantitatively reproduces the dynamics and energetics seen in atomistic molecular dynamics simulations of torque-driven γ-subunit rotation in the F1-ATPase rotary motor. The torsional elastic coefficients determined from the simulations agree with results from independent single-molecule experiments probing different segments of the γ-subunit, which resolves a long-lasting controversy. At steady rotational speeds of ∼ 1 kHz corresponding to experimental turnover, the calculated frictional dissipation of less than k(B)T per rotation is consistent with the high thermodynamic efficiency of the fully reversible motor. Without load, the maximum rotational speed during transitions between dwells is reached at ∼ 1 MHz. Energetic constraints dictate a unique pathway for the coupled rotations of the Fo and F1 rotary motors in ATP synthase, and explain the need for the finer stepping of the F1 motor in the mammalian system, as seen in recent experiments. Compensating for incommensurate eightfold and threefold rotational symmetries in Fo and F1, respectively, a significant fraction of the external mechanical work is transiently stored as elastic energy in the γ-subunit. The general framework developed here should be applicable to other molecular machines.

  20. Improve Motor System Efficiency for a Broad Range of Motors with MotorMaster+ International

    Energy Technology Data Exchange (ETDEWEB)

    None

    2005-05-01

    Available at no charge, MotorMaster+ International is designed to support motor systems improvement planning at industrial facilities by identifying the most cost-effective choice when deciding to repair or replace older motor models.

  1. Physics of protein motility and motor proteins

    Science.gov (United States)

    Kolomeisky, Anatoly B.

    2013-09-01

    Motor proteins are enzymatic molecules that transform chemical energy into mechanical motion and work. They are critically important for supporting various cellular activities and functions. In the last 15 years significant progress in understanding the functioning of motor proteins has been achieved due to revolutionary breakthroughs in single-molecule experimental techniques and strong advances in theoretical modelling. However, microscopic mechanisms of protein motility are still not well explained, and the collective efforts of many scientists are needed in order to solve these complex problems. In this special section the reader will find the latest advances on the difficult road to mapping motor proteins dynamics in various systems. Recent experimental developments have allowed researchers to monitor and to influence the activity of single motor proteins with a high spatial and temporal resolution. It has stimulated significant theoretical efforts to understand the non-equilibrium nature of protein motility phenomena. The latest results from all these advances are presented and discussed in this special section. We would like to thank the scientists from all over the world who have reported their latest research results for this special section. We are also grateful to the staff and editors of Journal of Physics: Condensed Matter for their invaluable help in handling all the administrative and refereeing activities. The field of motor proteins and protein motility is fast moving, and we hope that this collection of articles will be a useful source of information in this highly interdisciplinary area. Physics of protein motility and motor proteins contents Physics of protein motility and motor proteinsAnatoly B Kolomeisky Identification of unique interactions between the flexible linker and the RecA-like domains of DEAD-box helicase Mss116 Yuan Zhang, Mirkó Palla, Andrew Sun and Jung-Chi Liao The load dependence of the physical properties of a molecular motor

  2. General Motors Goes Metric

    Science.gov (United States)

    Webb, Ted

    1976-01-01

    Describes the program to convert to the metric system all of General Motors Corporation products. Steps include establishing policy regarding employee-owned tools, setting up training plans, and making arrangements with suppliers. (MF)

  3. Piezoelectric Rotary Tube Motor

    Science.gov (United States)

    Fisher, Charles D.; Badescu, Mircea; Braun, David F.; Culhane, Robert

    2011-01-01

    A custom rotary SQUIGGLE(Registered TradeMark) motor has been developed that sets new benchmarks for small motor size, high position resolution, and high torque without gear reduction. Its capabilities cannot be achieved with conventional electromagnetic motors. It consists of piezoelectric plates mounted on a square flexible tube. The plates are actuated via voltage waveforms 90 out of phase at the resonant frequency of the device to create rotary motion. The motors were incorporated into a two-axis postioner that was designed for fiber-fed spectroscopy for ground-based and space-based projects. The positioner enables large-scale celestial object surveys to take place in a practical amount of time.

  4. Congenital Ocular Motor Apraxia

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-06-01

    Full Text Available The clinical and neuroradiological findings, and long-term intellectual prognosis in 10 patients (4 boys and 6 girls with congenital ocular motor apraxia (COMA are reviewed by researchers at Tottori University, Yonago, Japan.

  5. Motor Carrier Crash Data -

    Data.gov (United States)

    Department of Transportation — Contains data on large trucks and buses involved in Federally reportable crashes as per Title 49 U.S.C. Part 390.5 (crashes involving a commercial motor vehicle, and...

  6. Split-phase motor running as capacitor starts motor and as capacitor run motor

    Directory of Open Access Journals (Sweden)

    Yahaya Asizehi ENESI

    2016-07-01

    Full Text Available In this paper, the input parameters of a single phase split-phase induction motor is taken to investigate and to study the output performance characteristics of capacitor start and capacitor run induction motor. The value of these input parameters are used in the design characteristics of capacitor run and capacitor start motor with each motor connected to rated or standard capacitor in series with auxiliary winding or starting winding respectively for the normal operational condition. The magnitude of capacitor that will develop maximum torque in capacitor start motor and capacitor run motor are investigated and determined by simulation. Each of these capacitors is connected to the auxiliary winding of split-phase motor thereby transforming it into capacitor start or capacitor run motor. The starting current and starting torque of the split-phase motor (SPM, capacitor run motor (CRM and capacitor star motor (CSM are compared for their suitability in their operational performance and applications.

  7. Recessively transmitted predominantly motor neuropathies.

    Science.gov (United States)

    Parman, Yeşim; Battaloğlu, Esra

    2013-01-01

    Recessively transmitted predominantly motor neuropathies are rare and show a severe phenotype. They are frequently observed in populations with a high rate of consanguineous marriages. At least 15 genes and six loci have been found to be associated with autosomal recessive CMT (AR-CMT) and X-linked CMT (AR-CMTX) and also distal hereditary motor neuronopathy (AR-dHMN). These disorders are genetically heterogeneous but the clinical phenotype is relatively homogeneous. Distal muscle weakness and atrophy predominating in the lower extremities, diminished or absent deep tendon reflexes, distal sensory loss, and pes cavus are the main clinical features of this disorder with occasional cranial nerve involvement. Although genetic diagnosis of some of subtypes of AR-CMT are now available, rapid advances in the molecular genetics and cell biology show a great complexity. Animal models for the most common subtypes of human AR-CMT disease provide clues for understanding the pathogenesis of CMT and also help to reveal possible treatment strategies of inherited neuropathies. This chapter highlights the clinical features and the recent genetic and biological findings in these disorders based on the current classification.

  8. Persistence of strain in motor-filament assemblies

    CERN Document Server

    Gopinath, Arvind; Mahadevan, L

    2015-01-01

    Crosslinked semi-flexible and flexible filaments that are actively deformed by molecular motors occur in various natural settings, such as the ordered eukaryotic flagellum, and the disordered cytoskeleton. The deformation of these composite systems is driven by active motor forces and resisted by passive filament elasticity, and structural constraints due to permanent cross-links. Using a mean field theory for a one-dimensional ordered system, we show that the combination of motor activity and finite filament extensibility yields a characteristic persistence length scale over which active strain decays. This decay length is set by the ability of motors to respond to combination of the weak extensional elasticity, passive shear resistance and the viscoelastic properties of the motor assembly, and generalizes the notion of persistence in purely thermal filaments to active systems.

  9. Knowledge and motor performance.

    Science.gov (United States)

    Kerr, R; Boucher, J L

    1992-06-01

    Traditionally, motor skill acquisition has implied that the performance of a given individual on a particular skill is dependent on the amount of prior practice of that skill. However, concepts such as schema theory, or kinetic formulae, or the strategic allocation of resources imply that, even when practising specific skills, performers gain knowledge about their own motor performance which can be used or applied to related or novel situations. An attempt was made to relate the performance of a complex psychomotor task to differing levels of motor skill expertise or knowledge (athlete and nonathlete). 20 subjects performed (1600 responses) on a novel pursuit or tracking task. Analysis indicated that the athletes performed significantly better. Their main advantage appeared to be more in their ability to control and produce fast, accurate movements than in their decision-making. Accepting Henry and Rogers' 1960 proposition that there is no such thing as a general motor ability or coordination factor does not imply that the only alternative is for all motor skills to be specific. It is argued that the differences in the present study arose from the athletes' greater knowledge (schema, kinetic formulae) related to their understanding of their own motor capabilities.

  10. Progress and perspective of the kinetochore-associated motor proteins

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The kinetochore is structurally composed of four layers. We know that three microtubule-based motor proteins such as CENP-E, dynein, and MCAK are located at the outmost region of the kinetochore. Experimentation of these motor functions betters our understanding of mitotic regulation, and chromosome movements in particular. With real-time studies of chromosome movements in live cells, we hope to illustrate the molecular mechanisms underlying mitotic regulation.

  11. Shape memory alloy based motor

    Indian Academy of Sciences (India)

    S V Sharma; M M Nayak; N S Dinesh

    2008-10-01

    Design and characterization of a new shape memory alloy wire based Poly Phase Motor has been reported in this paper. The motor can be used either in stepping mode or in servo mode of operation. Each phase of the motor consists of an SMA wire with a spring in series. The principle of operation of the poly phase motor is presented. The motor resembles a stepper motor in its functioning though the actuation principles are different and hence has been characterized similar to a stepper motor. The motor can be actuated in either direction with different phase sequencing methods, which are presented in this work. The motor is modelled and simulated and the results of simulations and experiments are presented. The experimental model of the motor is of dimension 150 mm square, 20 mm thick and uses SMA wire of 0·4 mm diameter and 125 mm of length in each phase.

  12. B13+: Photodriven Molecular Wankel Engine

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jin; Sergeeva, Alina P.; Sparta, Manuel; Alexandrova, Anastassia N.

    2012-07-09

    Synthetic molecular motors that are capable of delivering controlled movement upon energy input are one of the key building blocks in nanomachinery. The major energy sources of molecular motors are from chemical reactions, photon beams, or electric current, which are converted into mechanical forces through the excitation of the electronic states of the molecule. The energy scale of the electronic excitation is normally two orders of magnitude larger than the molecular vibrational frequencies. To reduce the heat dissipation and increase the energy utilization efficiency, a motor running purely on the electronic ground-state (GS) potential energy surfaces is highly desirable.

  13. Sensing with the Motor Cortex

    OpenAIRE

    Hatsopoulos, Nicholas G.; Suminski, Aaron J.

    2011-01-01

    The primary motor cortex is a critical node in the network of brain regions responsible for voluntary motor behavior. It has been less appreciated, however, that the motor cortex exhibits sensory responses in a variety of modalities including vision and somatosensation. We review current work that emphasizes the heterogeneity in sensori-motor responses in the motor cortex and focus on its implications for cortical control of movement as well as for brain-machine interface development.

  14. Nanoconfined catalytic Ångström-size motors

    Energy Technology Data Exchange (ETDEWEB)

    Colberg, Peter H., E-mail: pcolberg@chem.utoronto.ca; Kapral, Raymond, E-mail: rkapral@chem.utoronto.ca [Chemical Physics Theory Group, Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6 (Canada)

    2015-11-14

    Self-propelled chemically powered synthetic micron and nano-scale motors are being intensively studied because of the wide range of potential applications that exploit their directed motion. This paper considers even smaller Ångström-size synthetic motors. Such very small motors in bulk solution display effects arising from their self-propulsion. Recent experiments have shown that small-molecule catalysts and single enzyme molecules exhibit properties that have been attributed to their chemical activity. Molecular dynamics is used to investigate the properties of very small Ångström-size synthetic chemically powered sphere-dimer motors in a simple atomic-like solvent confined between walls separated by distances of tens of nanometers. Evidence for strong structural ordering of the motors between the walls, which reflects the finite size of solvent molecules and depends on solvent depletion forces, is provided. Dynamical properties, such as average motor velocity, orientational relaxation, and mean square displacement, are anisotropic and depend on the distance from the walls. This research provides information needed for potential applications that use molecular-scale motors in the complex confined geometries encountered in biology and the laboratory.

  15. Máquinas Moleculares Artificiais

    OpenAIRE

    Mariana F. A. N. Guterres; Celia M. Ronconi

    2009-01-01

    The past decade has seen a dramatic increase in the number and structural/functional complexity of the artificial molecular machines that have been designed. In particular, numerous improvements in the construction procedures have led to the development of molecular switches, nanovalves, molecular muscles, nanoelevators, and rotary motors powered by photochemical, chemical, and electrochemical energy. The aim of this work is to discuss the basic principles involved in the construction of arti...

  16. Cargo Transport by Two Coupled Myosin Va Motors on Actin Filaments and Bundles.

    Science.gov (United States)

    Ali, M Yusuf; Vilfan, Andrej; Trybus, Kathleen M; Warshaw, David M

    2016-11-15

    Myosin Va (myoVa) is a processive, actin-based molecular motor essential for intracellular cargo transport. When a cargo is transported by an ensemble of myoVa motors, each motor faces significant physical barriers and directional challenges created by the complex actin cytoskeleton, a network of actin filaments and actin bundles. The principles that govern the interaction of multiple motors attached to the same cargo are still poorly understood. To understand the mechanical interactions between multiple motors, we developed a simple in vitro model in which two individual myoVa motors labeled with different-colored Qdots are linked via a third Qdot that acts as a cargo. The velocity of this two-motor complex was reduced by 27% as compared to a single motor, whereas run length was increased by only 37%, much less than expected from multimotor transport models. Therefore, at low ATP, which allowed us to identify individual motor steps, we investigated the intermotor dynamics within the two-motor complex. The randomness of stepping leads to a buildup of tension in the linkage between motors-which in turn slows down the leading motor-and increases the frequency of backward steps and the detachment rate. We establish a direct relationship between the velocity reduction and the distribution of intermotor distances. The analysis of run lengths and dwell times for the two-motor complex, which has only one motor engaged with the actin track, reveals that half of the runs are terminated by almost simultaneous detachment of both motors. This finding challenges the assumptions of conventional multimotor models based on consecutive motor detachment. Similar, but even more drastic, results were observed with two-motor complexes on actin bundles, which showed a run length that was even shorter than that of a single motor.

  17. An autonomous chemically fuelled small-molecule motor

    Science.gov (United States)

    Wilson, Miriam R.; Solà, Jordi; Carlone, Armando; Goldup, Stephen M.; Lebrasseur, Nathalie; Leigh, David A.

    2016-06-01

    Molecular machines are among the most complex of all functional molecules and lie at the heart of nearly every biological process. A number of synthetic small-molecule machines have been developed, including molecular muscles, synthesizers, pumps, walkers, transporters and light-driven and electrically driven rotary motors. However, although biological molecular motors are powered by chemical gradients or the hydrolysis of adenosine triphosphate (ATP), so far there are no synthetic small-molecule motors that can operate autonomously using chemical energy (that is, the components move with net directionality as long as a chemical fuel is present). Here we describe a system in which a small molecular ring (macrocycle) is continuously transported directionally around a cyclic molecular track when powered by irreversible reactions of a chemical fuel, 9-fluorenylmethoxycarbonyl chloride. Key to the design is that the rate of reaction of this fuel with reactive sites on the cyclic track is faster when the macrocycle is far from the reactive site than when it is near to it. We find that a bulky pyridine-based catalyst promotes carbonate-forming reactions that ratchet the displacement of the macrocycle away from the reactive sites on the track. Under reaction conditions where both attachment and cleavage of the 9-fluorenylmethoxycarbonyl groups occur through different processes, and the cleavage reaction occurs at a rate independent of macrocycle location, net directional rotation of the molecular motor continues for as long as unreacted fuel remains. We anticipate that autonomous chemically fuelled molecular motors will find application as engines in molecular nanotechnology.

  18. Magnetostrictive direct drive motor

    Science.gov (United States)

    Naik, Dipak; Dehoff, P. H.

    1991-01-01

    Highly magnetostrictive materials such as Tb.3Dy.7Fe2, commercially known as TERFENOL-D, have been used to date in a variety of devices such as high power actuators and linear motors. The larger magnetostriction available in twinned single crystal TERFENOL-D, approx. 2000 ppm at moderate magnetic field strengths, makes possible a new generation of magnetomechanical devices. NASA researchers are studying the potential of this material as the basis for a direct microstepping rotary motor with torque densities on the order of industrial hydraulics and five times greater than that of the most efficient, high power electric motors. Such a motor would be a micro-radian stepper, capable of precision movements and self-braking in the power-off state. Innovative mechanical engineering techniques are juxtaposed on proper magnetic circuit design to reduce losses in structural flexures, inertias, thermal expansions, eddy currents, and magneto-mechanical coupling, thus optimizing motor performance and efficiency. Mathematical models are presented, including magnetic, structural, and both linear and nonlinear dynamic calculations and simulations. In addition, test results on prototypes are presented.

  19. Dualities in the analysis of phage DNA packaging motors

    Science.gov (United States)

    Serwer, Philip; Jiang, Wen

    2012-01-01

    The DNA packaging motors of double-stranded DNA phages are models for analysis of all multi-molecular motors and for analysis of several fundamental aspects of biology, including early evolution, relationship of in vivo to in vitro biochemistry and targets for anti-virals. Work on phage DNA packaging motors both has produced and is producing dualities in the interpretation of data obtained by use of both traditional techniques and the more recently developed procedures of single-molecule analysis. The dualities include (1) reductive vs. accretive evolution, (2) rotation vs. stasis of sub-assemblies of the motor, (3) thermal ratcheting vs. power stroking in generating force, (4) complete motor vs. spark plug role for the packaging ATPase, (5) use of previously isolated vs. new intermediates for analysis of the intermediate states of the motor and (6) a motor with one cycle vs. a motor with two cycles. We provide background for these dualities, some of which are under-emphasized in the literature. We suggest directions for future research. PMID:23532204

  20. Advanced AC Motor Control

    Energy Technology Data Exchange (ETDEWEB)

    Kazmierkowski, M.P. [Institute of Control and Industrial Electronics, Warsaw University of Technology, Warszawa (Poland)

    1997-12-31

    In this paper a review of control methods for high performance PWM inverter-fed induction motor drives is presented. Starting from the description of an induction motor by the help of the space vectors, three basic control strategic are discussed. As first, the most popular Field Oriented Control (FOC) is described. Secondly, the Direct Torque and Flux vector Control (DTFC) method, which - in contrast to FOC - depart from idea of coordinate transformation and analogy with DC motor, is briefly characterized. The last group is based on Feedback Linearization Control (FLC) and can be easy combined with sliding mode control. The simulation and experimental oscillograms that illustrate the performance of the discussed control strategies are shown. (orig.) 35 refs.

  1. A Flashing Model for Transport of Brownian Motors

    Institute of Scientific and Technical Information of China (English)

    赵同军; 展永; 吴建海; 王永宏

    2002-01-01

    A flashing coloured noise model is proposed to describe the motion of a molecular motor. In this model,the overdamped Brownian particle moves in an asymmetric periodic potential with a tashing Ornstein-Ulenbeck coloured noise. The relationship between the current and the parameters-such as the intensity, the correlation time of coloured noise and the flip rate of the noise-is discussed using the Monte Carlo simulation method.Current reversal occurs with the change of the correlation time and the flip rate of coloured noise, which may be related to the directed motion and the current reversal of molecular motors.

  2. Mechanical design of electric motors

    CERN Document Server

    Tong, Wei

    2014-01-01

    Rapid increases in energy consumption and emphasis on environmental protection have posed challenges for the motor industry, as has the design and manufacture of highly efficient, reliable, cost-effective, energy-saving, quiet, precisely controlled, and long-lasting electric motors.Suitable for motor designers, engineers, and manufacturers, as well as maintenance personnel, undergraduate and graduate students, and academic researchers, Mechanical Design of Electric Motors provides in-depth knowledge of state-of-the-art design methods and developments of electric motors. From motor classificati

  3. Efficiency at Maximum Power of Interacting Molecular Machines

    DEFF Research Database (Denmark)

    Golubeva, Natalia; Imparato, Alberto

    2012-01-01

    We investigate the efficiency of systems of molecular motors operating at maximum power. We consider two models of kinesin motors on a microtubule: for both the simplified and the detailed model, we find that the many-body exclusion effect enhances the efficiency at maximum power of the many- motor...... system, with respect to the single motor case. Remarkably, we find that this effect occurs in a limited region of the system parameters, compatible with the biologically relevant range....

  4. Induction motor starting current

    Energy Technology Data Exchange (ETDEWEB)

    Arneaud, J.M.; Langman, R.A. [Tasmania Univ., Hobart, TAS (Australia)

    1995-12-31

    Large errors may occur if leakage path saturation is neglected when reduced-voltage test results are used to predict the direct-on-line starting current of induction motors. The results of applying three existing and two new methods for starting current prediction are compared with test data from 52 motors. A quantitative assessment is made of the probable reduction in error that would be achieved by increasing the number of available sets of reduced-voltage, locked rotor test results or by including slot design data. Guidelines are given for selecting an appropriate predictive method. (author). 4 tabs., 1 fig., 6 refs.

  5. Step Motor Control System

    Institute of Scientific and Technical Information of China (English)

    ZhangShuochengt; WangDan; QiaoWeimin; JingLan

    2003-01-01

    All kinds of step motors and servomotors are widely used in CSR control system, such as many vacuum valves control that set on the HIRFL-CSR; all kinds of electric switches and knobs of ECR Ion Source; equipment of CSR Beam Diagnostics and a lot of large equipment like Inside Gun Toroid and Collector Toroid of HIRFL. A typical control system include up to 32 16-I/O Control boards, and each 16-I/O Control board can control 4 motors at the same time (including 8 Limit Switches).

  6. Transformers and motors

    CERN Document Server

    Shultz, George

    1991-01-01

    Transformers and Motors is an in-depth technical reference which was originally written for the National Joint Apprenticeship Training Committee to train apprentice and journeymen electricians. This book provides detailed information for equipment installation and covers equipment maintenance and repair. The book also includes troubleshooting and replacement guidelines, and it contains a minimum of theory and math.In this easy-to-understand, practical sourcebook, you'll discover:* Explanations of the fundamental concepts of transformers and motors* Transformer connections and d

  7. Macroscopic transport by synthetic molecular machines

    NARCIS (Netherlands)

    Berna, J; Leigh, DA; Lubomska, M; Mendoza, SM; Perez, EM; Rudolf, P; Teobaldi, G; Zerbetto, F

    2005-01-01

    Nature uses molecular motors and machines in virtually every significant biological process, but demonstrating that simpler artificial structures operating through the same gross mechanisms can be interfaced with - and perform physical tasks in - the macroscopic world represents a significant hurdle

  8. 46 CFR 169.684 - Overcurrent protection for motors and motor branch circuits.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Overcurrent protection for motors and motor branch... motors and motor branch circuits. (a) Except as provided in paragraph (d) of this section, each motor... motor that is responsive to motor current or to both motor current and temperature may be used. (b)...

  9. Method for assessing motor insulation on operating motors

    Science.gov (United States)

    Kueck, John D.; Otaduy, Pedro J.

    1997-01-01

    A method for monitoring the condition of electrical-motor-driven devices. The method is achieved by monitoring electrical variables associated with the functioning of an operating motor, applying these electrical variables to a three phase equivalent circuit and determining non-symmetrical faults in the operating motor based upon symmetrical components analysis techniques.

  10. General Motors sidestream separator

    Energy Technology Data Exchange (ETDEWEB)

    Tessier, R.J.

    1981-01-01

    On February 15, 1980, the United States Environmental Protection Agency, acting pursuant to Paragraph 113(D) (4) of the Clean Air Act, issued to General Motors an innovative technology order covering fifteen coal-fired spreader-stoker boilers located at six General Motors plants in Ohio. The purpose and effect of this order was to permit General Motors time to develop a new, innovative technique for controlling particulate emissions from the specified boilers before compliance with the federally approved Ohio particulate control regulation was required. This new technology was christened, The Sidestream Separator, by General Motors. It provides a highly cost effective means of reducing particulate emissions below levels currently obtainable with conventionally used high efficiency mechanical collectors. These improvements could prove to be of substantial benefit to many industrial facilities with spreader-stoker coal-fired boilers that cannot be brought into compliance with applicble air pollution regulations except by application of far more expensive and unwieldly electrostatic precipitators (ESP's) or fabric filters (baghouses).

  11. Motor Vehicle Safety

    Science.gov (United States)

    ... to prevent these crashes is one part of motor vehicle safety. Here are some things you can do to be safer on the road: Make sure your vehicle is safe and in working order Use car seats for children Wear your seat belt Don' ...

  12. Aprendizaje y desarrollo motor

    OpenAIRE

    Guillén Guillén, Eva I.

    2006-01-01

    El desarrollo evolutivo general del niño/a en relación con los procesos de maduración motora, procesos de aprendizaje y desarrollo motor. Técnicas de aprendizaje. Técnica de solución de conflictos. Balances musculares.

  13. Gas-operated motor systems

    Energy Technology Data Exchange (ETDEWEB)

    Rilett, J.W.

    1980-09-30

    A gas-operated motor system of the stored energy type-as disclosed in U.S. Pat. No. 4,092,830-in which the gas exhausted from the motor is ducted to a chamber during operation of the motor and thereafter compressed back into the gas reservoir vessel. Recompression may be achieved, e.g., by providing the exhaust gas chamber with a movable piston, or by running the motor in the reverse mode as a compressor.

  14. MOTORIC STIMULATION RELATED TO FINE MOTORIC DEVELOPMENT ON CHILD

    Directory of Open Access Journals (Sweden)

    Mira Triharini

    2017-07-01

    Full Text Available Introduction: Motor developmental stimulation is an activity undertaken to stimulate the children basic skills and so they can grow and develop optimally. Children who obtain a direct stimulus will grow faster than who get less stimulus. Mother’s behavior of stimulation is very important for children, it is considering as the basic needs of children and it must be fulfilled. Providing good stimulation could optimize fine motor development in children. The purpose of this study was to analyze mother’s behavior about motor stimulation with fine motor development in toddler age 4-5 years old. Method: Design have been  used in this study was cross sectional. Population were mothers and their toddler in Group A of Dharma Wanita Persatuan Driyorejo Gresik Preschool. Sample were 51 respondents recruited by using purposive sampling technique according to inclusion and exclusion criteria. The independent variable was mother’s behavior about motor stimulation whereas dependent variable was fine motor development in toddler. The data were collected using questionnaire and conducting observation on fine motor development based on Denver Development Screening Test (DDST. Data then analyzed using Spearman Rho (r test to find relation between mother’s behaviors about stimulation motor on their toddler fine motor development. Result: Results  of this study showed that there were correlations between mother’s knowledge and fine motor development in toddler (p=0.000, between mother’s attitude and fine motor development in toddler (p=0.000, and between mother’s actions and fine motor development in toddler (p=0.000. Analysis: In sort study found that there were relation between fine motor development and mother’s behavior. Discussion: Therefore mother’s behavior needed to be improved. Further research about stimulation motor and fine motor development aspects in toddler is required.

  15. Crosstalk between non-processive myosin motors mediated by the actin filament elasticity

    CERN Document Server

    Farago, Oded

    2011-01-01

    Many biological processes involve the action of molecular motors that interact with the cell cytoskeleton. Some processes, such as the transport of cargoes is achieved mainly by the action of individual motors. Other, such as cell motility and division, require the cooperative work of many motors. Collective motor dynamics can be quite complex and unexpected. One beautiful example is the bidirectional ("back and forth") motion of filaments which is induced when the motors within a group exert forces in opposite directions. This review tackles the puzzle emerging from a recent experimental work in which it has been shown that the characteristic reversal times of the bidirectional motion are practically independent of the number of motors. This result is in a striking contradiction with existing theoretical models that predict an exponential growth of the reversal times with the size of the system. We argue that the solution to this puzzle may be the crosstalk between the motors which is mediated by the elastic...

  16. Piezoelectric Torsional Vibration Driven Motor

    Science.gov (United States)

    2000-10-29

    20 which can provide large amplitude rotational motion with a high torque. 21 Piezoelectric ultrasonic motors have been developed using traveling...Motor for High Torque", T. S. Glenn, W.G. Hagwood, SPIE Volume 3041, 4 1997. These piezoelectric ultrasonic motors are of limited application

  17. Experiments with a DC Motor

    Science.gov (United States)

    Kraftmakher, Yaakov

    2010-01-01

    Experiments with an electric motor provide good opportunity to demonstrate some basic laws of electricity and magnetism. The aim of the experiments with a low-power dc motor is to show how the motor approaches its steady rotation and how its torque, mechanical power and efficiency depend on the rotation velocity. The tight relationship between the…

  18. Sufficient conditions for the additivity of stall forces generated by multiple filaments or motors

    Science.gov (United States)

    Bameta, Tripti; Das, Dipjyoti; Das, Dibyendu; Padinhateeri, Ranjith; Inamdar, Mandar M.

    2017-02-01

    Molecular motors and cytoskeletal filaments work collectively most of the time under opposing forces. This opposing force may be due to cargo carried by motors or resistance coming from the cell membrane pressing against the cytoskeletal filaments. Some recent studies have shown that the collective maximum force (stall force) generated by multiple cytoskeletal filaments or molecular motors may not always be just a simple sum of the stall forces of the individual filaments or motors. To understand this excess or deficit in the collective force, we study a broad class of models of both cytoskeletal filaments and molecular motors. We argue that the stall force generated by a group of filaments or motors is additive, that is, the stall force of N number of filaments (motors) is N times the stall force of one filament (motor), when the system is reversible at stall. Conversely, we show that this additive property typically does not hold true when the system is irreversible at stall. We thus present a novel and unified understanding of the existing models exhibiting such non-addivity, and generalise our arguments by developing new models that demonstrate this phenomena. We also propose a quantity similar to thermodynamic efficiency to easily predict this deviation from stall-force additivity for filament and motor collectives.

  19. Coordinated switching of bacterial flagellar motors: evidence for direct motor-motor coupling?

    Science.gov (United States)

    Hu, Bo; Tu, Yuhai

    2013-01-01

    The swimming of Escherichia coli is powered by its multiple flagellar motors. Each motor spins either clockwise (CW) or counterclockwise (CCW), under the control of an intracellular regulator, CheY-P. There can be two mechanisms (extrinsic and intrinsic) to coordinate the switching of bacterial motors. The extrinsic one arises from the fact that different motors in the same cell sense a common input (CheY-P) which fluctuates near the motors' response threshold. An alternative, intrinsic mechanism is direct motor-motor coupling which makes synchronized switching energetically favorable. Here, we develop simple models for both mechanisms and uncover their different hallmarks. A quantitative comparison to the recent experiments suggest that the direct coupling mechanism may be accountable for the observed sharp correlation between motors in a single E. coli. Possible origins of this coupling (e.g., hydrodynamic interaction) are discussed. PMID:25167320

  20. Persistence of activity in noisy motor-filament assemblies

    CERN Document Server

    Chelakkot, Raghunath; Mahadevan, L

    2015-01-01

    Long, elastic filaments cross-linked and deformed by active molecular motors occur in various natural settings. The overall macroscopic mechanical response of such a composite network depends on the coupling between the active and the passive properties of the underlying constituents and nonlocal interactions between different parts of the composite. In a simple one dimensional system, using a mean field model, it has been shown that the combination of motor activity and finite filament extensibility yields a persistence length scale over which strain decays. Here we study a similar system, in the complementary limit of strong noise and moderate extensibility, using Brownian multi-particle collision dynamics-based numerical simulations that includes the coupling between motor kinetics and local filament extensibility. While the numerical model shows deviations from the mean field predictions due to the presence of strong active noise caused by the variations in individual motor activity, several qualitative f...

  1. Motor unit changes in normal aging: a brief review.

    Science.gov (United States)

    Tudoraşcu, Iulia; Sfredel, Veronica; Riza, Anca Lelia; Dănciulescu Miulescu, Rucsandra; Ianoşi, Simona Laura; Dănoiu, Suzana

    2014-01-01

    Aging is explored by multiple lines of research, in a pursuit of understanding this natural process. The motor response is usually the main dependent variable in studies regarding physical or cognitive decline in aging. It is therefore critical to understand how the motor function changes with age. The present review, aims at presenting briefly some of the most recently published works in the field, focusing on the three key components of the motor unit. The changes that the skeletal muscle undergoes aging sarcopenia, alteration of fiber type distribution and also intimate metabolic transformations. The neuromuscular junction suffers at cellular and molecular level, with possible implications of various cell components, mediators and oxidative stress. Motoneuron loss and change in their physiological properties accompany remodeling in the motor units. The applicability of knowledge in this field lies in possible interventions intended to counteract these age-related losses.

  2. Run-and-tumble dynamics of cytoskeletal motor proteins

    CERN Document Server

    Hafner, Anne E; Rieger, Heiko; Shaebani, M Reza

    2016-01-01

    Cytoskeletal motor proteins are involved in major intracellular transport processes which are vital for maintaining appropriate cellular function. The motor exhibits distinct states of motility: active motion along filaments, and effectively stationary phase in which it detaches from the filaments and performs passive diffusion in the vicinity of the detachment point due to cytoplasmic crowding. The transition rates between motion and pause phases are asymmetric in general, and considerably affected by changes in environmental conditions which influences the efficiency of cargo delivery to specific targets. By considering the motion of molecular motor on a single filament as well as a dynamic filamentous network, we present an analytical model for the dynamics of self-propelled particles which undergo frequent pause phases. The interplay between motor processivity, structural properties of filamentous network, and transition rates between the two states of motility drastically changes the dynamics: multiple t...

  3. A synthetic DNA motor that transports nanoparticles along carbon nanotubes

    Science.gov (United States)

    Cha, Tae-Gon; Pan, Jing; Chen, Haorong; Salgado, Janette; Li, Xiang; Mao, Chengde; Choi, Jong Hyun

    2014-01-01

    Intracellular protein motors have evolved to perform specific tasks critical to the function of cells such as intracellular trafficking and cell division. Kinesin and dynein motors, for example, transport cargoes in living cells by walking along microtubules powered by adenosine triphosphate hydrolysis. These motors can make discrete 8 nm centre-of-mass steps and can travel over 1 µm by changing their conformations during the course of adenosine triphosphate binding, hydrolysis and product release. Inspired by such biological machines, synthetic analogues have been developed including self-assembled DNA walkers that can make stepwise movements on RNA/DNA substrates or can function as programmable assembly lines. Here, we show that motors based on RNA-cleaving DNA enzymes can transport nanoparticle cargoes--CdS nanocrystals in this case--along single-walled carbon nanotubes. Our motors extract chemical energy from RNA molecules decorated on the nanotubes and use that energy to fuel autonomous, processive walking through a series of conformational changes along the one-dimensional track. The walking is controllable and adapts to changes in the local environment, which allows us to remotely direct `go' and `stop' actions. The translocation of individual motors can be visualized in real time using the visible fluorescence of the cargo nanoparticle and the near-infared emission of the carbon-nanotube track. We observed unidirectional movements of the molecular motors over 3 µm with a translocation velocity on the order of 1 nm min-1 under our experimental conditions.

  4. Split-phase motor running as capacitor starts motor and as capacitor run motor

    OpenAIRE

    2016-01-01

    In this paper, the input parameters of a single phase split-phase induction motor is taken to investigate and to study the output performance characteristics of capacitor start and capacitor run induction motor. The value of these input parameters are used in the design characteristics of capacitor run and capacitor start motor with each motor connected to rated or standard capacitor in series with auxiliary winding or starting winding respectively for the normal operational condition. The ma...

  5. Random intermittent search and the tug-of-war model of motor-driven transport

    KAUST Repository

    Newby, Jay

    2010-04-16

    We formulate the \\'tug-of-war\\' model of microtubule cargo transport by multiple molecular motors as an intermittent random search for a hidden target. A motor complex consisting of multiple molecular motors with opposing directional preference is modeled using a discrete Markov process. The motors randomly pull each other off of the microtubule so that the state of the motor complex is determined by the number of bound motors. The tug-of-war model prescribes the state transition rates and corresponding cargo velocities in terms of experimentally measured physical parameters. We add space to the resulting Chapman-Kolmogorov (CK) equation so that we can consider delivery of the cargo to a hidden target at an unknown location along the microtubule track. The target represents some subcellular compartment such as a synapse in a neuron\\'s dendrites, and target delivery is modeled as a simple absorption process. Using a quasi-steady-state (QSS) reduction technique we calculate analytical approximations of the mean first passage time (MFPT) to find the target. We show that there exists an optimal adenosine triphosphate (ATP) concentration that minimizes the MFPT for two different cases: (i) the motor complex is composed of equal numbers of kinesin motors bound to two different microtubules (symmetric tug-of-war model) and (ii) the motor complex is composed of different numbers of kinesin and dynein motors bound to a single microtubule (asymmetric tug-of-war model). © 2010 IOP Publishing Ltd.

  6. Control linear motor with DSP

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Han

    2003-06-15

    This book consists of control linear motor with DSP, which is composed of two parts. The title of the first part is control Algorithm and software with introduction and tracking controller, drive profile on decision of motion time, floating point DSP and quantization effect, motion override Algorithm and drive profile summary, design of digital controller on design for controller structure and analysis of PID control Loop and Motor turning, design for IIR digital filter and protocol structure for communication wit host. The second part describes control hardware, which mentions Linear motor and Amplifier, motor and power supply, DSP board and interface, control of Micro Linear Stepping Motor and conclusion.

  7. Acute exercise improves motor memory

    DEFF Research Database (Denmark)

    Skriver, Kasper Christen; Roig, Marc; Lundbye-Jensen, Jesper

    2014-01-01

    We have recently shown that a single bout of acute cardiovascular exercise improves motor skill learning through an optimization of long-term motor memory. Here we expand this previous finding, to explore potential exercise-related biomarkers and their association with measures of motor memory...... practice whereas lactate correlated with better retention 1 hour as well as 24 hours and 7 days after practice. Thus, improvements in motor skill acquisition and retention induced by acute cardiovascular exercise are associated with increased concentrations of biomarkers involved in memory and learning...... processes. More mechanistic studies are required to elucidate the specific role of each biomarker in the formation of motor memory....

  8. Magnetostrictive direct drive motors

    Science.gov (United States)

    Naik, Dipak; Dehoff, P. H.

    1992-01-01

    A new rare earth alloy, Terfenol-D, combines low frequency operation and extremely high energy density with high magnetostriction. Its material properties make it suitable as a drive element for actuators requiring high output torque. The high strains, the high forces and the high controllability of Terfenol alloys provide a powerful and challenging basis for new ways to generate motion in actuators. Two prototypes of motors using Terfenol-D rods were developed at NASA Goddard. The basic principles of operation are provided of the motor along with other relevant details. A conceptual design of a torque limiting safety clutch/brake under development is illustrated. Also, preliminary design drawings of a linear actuator using Terfenol-D is shown.

  9. Understanding social motor coordination.

    Science.gov (United States)

    Schmidt, R C; Fitzpatrick, Paula; Caron, Robert; Mergeche, Joanna

    2011-10-01

    Recently there has been much interest in social coordination of motor movements, or as it is referred to by some researchers, joint action. This paper reviews the cognitive perspective's common coding/mirror neuron theory of joint action, describes some of its limitations and then presents the behavioral dynamics perspective as an alternative way of understanding social motor coordination. In particular, behavioral dynamics' ability to explain the temporal coordination of interacting individuals is detailed. Two experiments are then described that demonstrate how dynamical processes of synchronization are apparent in the coordination underlying everyday joint actions such as martial art exercises, hand-clapping games, and conversations. The import of this evidence is that emergent dynamic patterns such as synchronization are the behavioral order that any neural substrate supporting joint action (e.g., mirror systems) would have to sustain.

  10. Ironless armature torque motor

    Science.gov (United States)

    Fisher, R. L.

    1972-01-01

    Four iron-less armature torque motors, four Hall device position sensor assemblies, and two test fixtures were fabricated. The design approach utilized samarium cobalt permanent magnets, a large airgap, and a three-phase winding in a stationary ironless armature. Hall devices were employed to sense rotor position. An ironless armature torque motor having an outer diameter of 4.25 inches was developed to produce a torque constant of 65 ounce-inches per ampere with a resistance of 20.5 ohms. The total weight, including structural elements, was 1.58 pounds. Test results indicated that all specifications were met except for generated voltage waveform. It is recommended that investigations be made concerning the generated voltage waveform to determine if it may be improved.

  11. 350 KVA motor generators

    CERN Multimedia

    CERN PhotoLab

    1974-01-01

    Each logic circuit in the central computers consumes only a fraction of a watt: however, the final load constituted by many such circuits plus peripheral equipment is nearly half a million watts. Shown here are two 350 KVA motor generators used to convert 50 Hz mains to 60 Hz (US standard). Flywheels on the M.G. shafts remove power dropouts of up to 0.5 s.

  12. The St. Louis Motor

    Science.gov (United States)

    Greenslade, Thomas B.

    2011-10-01

    The St. Louis Motor, invented in 1909, is unique among physics apparatus for being named for a geographical place rather than a physicist. The sturdy little device (Fig. 1) has never been out of production. Any older school or physics department that has not done a catastrophic housecleaning in the last 20 years will certainly have a small flock of them in the back room.

  13. Motor neurone disease.

    Science.gov (United States)

    2016-03-23

    Essential facts Motor neurone disease describes a group of related diseases, affecting the neurones in the brain and spinal cord. Progressive, incurable and life-limiting, MND is rare, with about 1,100 people developing it each year in the UK and up to 5,000 people affected at any one time. One third of people will die within a year of diagnosis and more than half within two years. About 5% to 10% are alive at ten years.

  14. An Electrostatic Stepper Motor

    Science.gov (United States)

    Partington, E. C.; Wong, Edward Chun Kay; Bullough, W. A.

    This paper describes a new concept in pulse controlled motor and precision linear actuator techniques. Piezo translators [PZT] employed to provide reciprocating primary motion are connected to a load via a controllable electrorheological fluid [ERF] clutch to form a programmable speed and step-width drive. Ideal considerations are used to quantify the limiting potential of the drive and details are given of its development and progress.

  15. Lumbosacral motor polyneuropathy

    Directory of Open Access Journals (Sweden)

    S. A. Malmberg

    2012-01-01

    Full Text Available The case of lumbosacral motor neuropathy (LSMN in 15-yers old patient with diabetes mellitus (type I is presented. Clinical and electromyographical patterns are considered and effectiveness of corticosteroid therapy is estimated. The differential features and taxonomic position of LSMN and chronic inflammatory demyelinating polyneuropathy (CIDP are discussed. The necessity of some liberalization of CIDP diagnostic criteria is demonstrated.

  16. Motor Fuel Excise Taxes

    Energy Technology Data Exchange (ETDEWEB)

    2015-09-01

    A new report from the National Renewable Energy Laboratory (NREL) explores the role of alternative fuels and energy efficient vehicles in motor fuel taxes. Throughout the United States, it is common practice for federal, state, and local governments to tax motor fuels on a per gallon basis to fund construction and maintenance of our transportation infrastructure. In recent years, however, expenses have outpaced revenues creating substantial funding shortfalls that have required supplemental funding sources. While rising infrastructure costs and the decreasing purchasing power of the gas tax are significant factors contributing to the shortfall, the increased use of alternative fuels and more stringent fuel economy standards are also exacerbating revenue shortfalls. The current dynamic places vehicle efficiency and petroleum use reduction polices at direct odds with policies promoting robust transportation infrastructure. Understanding the energy, transportation, and environmental tradeoffs of motor fuel tax policies can be complicated, but recent experiences at the state level are helping policymakers align their energy and environmental priorities with highway funding requirements.

  17. Dyspraxia, motor function and visual-motor integration in autism.

    Science.gov (United States)

    Miller, M; Chukoskie, L; Zinni, M; Townsend, J; Trauner, D

    2014-08-01

    This project assessed dyspraxia in high-functioning school aged children with autism with a focus on Ideational Praxis. We examined the association of specific underlying motor function including eye movement with ideational dyspraxia (sequences of skilled movements) as well as the possible role of visual-motor integration in dyspraxia. We found that compared to IQ-, sex- and age-matched typically developing children, the children with autism performed significantly worse on: Ideational and Buccofacial praxis; a broad range of motor tests, including measures of simple motor skill, timing and accuracy of saccadic eye movements and motor coordination; and tests of visual-motor integration. Impairments in individual children with autism were heterogeneous in nature, although when we examined the praxis data as a function of a qualitative measure representing motor timing, we found that children with poor motor timing performed worse on all praxis categories and had slower and less accurate eye movements while those with regular timing performed as well as typical children on those same tasks. Our data provide evidence that both motor function and visual-motor integration contribute to dyspraxia. We suggest that dyspraxia in autism involves cerebellar mechanisms of movement control and the integration of these mechanisms with cortical networks implicated in praxis.

  18. Cooperative effects enhance the transport properties of molecular spider teams

    CERN Document Server

    Rank, Matthias; Frey, Erwin

    2013-01-01

    Molecular spiders are synthetic molecular motors based on DNA nanotechnology. While natural molecular motors have evolved towards very high efficiency, it remains a major challenge to develop efficient designs for man-made molecular motors. Inspired by biological motor proteins like kinesin and myosin, molecular spiders comprise a body and several legs. The legs walk on a lattice that is coated with substrate which can be cleaved catalytically. We propose a novel molecular spider design in which n spiders form a team. Our theoretical considerations show that coupling several spiders together alters the dynamics of the resulting team significantly. Although spiders operate at a scale where diffusion is dominant, spider teams can be tuned to behave nearly ballistic, which results in fast and predictable motion. Based on the separation of time scales of substrate and product dwell times, we develop a theory which utilises equivalence classes to coarse-grain the micro-state space. In addition, we calculate diffus...

  19. 77 FR 11598 - Thermal Overload Protection for Electric Motors on Motor-Operated Valves

    Science.gov (United States)

    2012-02-27

    ... COMMISSION Thermal Overload Protection for Electric Motors on Motor-Operated Valves AGENCY: Nuclear... for Electric Motors on Motor-Operated Valves.'' This regulatory guide describes a method acceptable to... devices that are integral with the motor starter for electric motors on motor-operated valves....

  20. Segmented motor drive - with multi-phase induction motor

    DEFF Research Database (Denmark)

    Bendixen, Flemming Buus

    This PhD project commences in modulation of motor drives, i.e. having the advantage of reducing the number of variants and improves the system reliability at error situations. Four different motor drive topologies with modular construction as common denominator are compared on a general level....... The multi-phase motor is selected for further analysis. The project is limited to examine if increasing the number of phases can improve the characteristics for induction motor drives. In the literature it is demonstrated that torque production in a six-phase motor can be increased, if a 3rd harmonic...... current with 1/6 amplitude is added to the 1st harmonic current. This claim is verified and the optimization of the motor design is extended to, beyond the stator tooth width, also to include the inner diameter of the stator. This means that the lamination sheet is optimized according to two geometrical...

  1. Promoting Neuroplasticity for Motor Rehabilitation After Stroke: Considering the Effects of Aerobic Exercise and Genetic Variation on Brain-Derived Neurotrophic Factor

    OpenAIRE

    Mang, Cameron S.; Campbell, Kristin L.; Ross, Colin J.D.; Boyd, Lara A.

    2013-01-01

    Recovery of motor function after stroke involves relearning motor skills and is mediated by neuroplasticity. Recent research has focused on developing rehabilitation strategies that facilitate such neuroplasticity to maximize functional outcome poststroke. Although many molecular signaling pathways are involved, brain-derived neurotrophic factor (BDNF) has emerged as a key facilitator of neuroplasticity involved in motor learning and rehabilitation after stroke. Thus, rehabilitation strategie...

  2. 75 FR 76692 - Federal Motor Vehicle Safety Standards; Small Business Impacts of Motor Vehicle Safety

    Science.gov (United States)

    2010-12-09

    ..., and 571 Federal Motor Vehicle Safety Standards; Small Business Impacts of Motor Vehicle Safety AGENCY... passenger vehicles, trucks, buses, trailers, incomplete vehicles, motorcycles, and motor vehicle...

  3. Steps in the bacterial flagellar motor.

    Directory of Open Access Journals (Sweden)

    Thierry Mora

    2009-10-01

    Full Text Available The bacterial flagellar motor is a highly efficient rotary machine used by many bacteria to propel themselves. It has recently been shown that at low speeds its rotation proceeds in steps. Here we propose a simple physical model, based on the storage of energy in protein springs, that accounts for this stepping behavior as a random walk in a tilted corrugated potential that combines torque and contact forces. We argue that the absolute angular position of the rotor is crucial for understanding step properties and show this hypothesis to be consistent with the available data, in particular the observation that backward steps are smaller on average than forward steps. We also predict a sublinear speed versus torque relationship for fixed load at low torque, and a peak in rotor diffusion as a function of torque. Our model provides a comprehensive framework for understanding and analyzing stepping behavior in the bacterial flagellar motor and proposes novel, testable predictions. More broadly, the storage of energy in protein springs by the flagellar motor may provide useful general insights into the design of highly efficient molecular machines.

  4. Adequate sizing and motor exploitation: Motor energy management

    Directory of Open Access Journals (Sweden)

    Kostić Miloje M.

    2011-01-01

    Full Text Available Motor energy management includes adequate sizing, control and improvement of electric energy quality, i.e. voltage quality (reducing voltage unbalance and harmonics distortion, and the proper maintenance. The specific motor price per kW is approximately constant for motors rated from 5 kW to 20 kW. By adequate sizing, or by proper replacement of the old motor with the new one, with rated output power reduced by 20% to 50% the smaller motor will be also cheaper by 20% to 50%. When the 22 kW motor is replaced with the new 15 kW that costs 64% of the price of a new 22 kW motor, the efficiency is increased by 3.6% (Example in paper. On the basis of our investigation results, it is confirmed that there are significant possibilities for energy savings by setting voltage values within the ±5% voltage band (Un±5%, since more than 80% induction motors are under loaded (£70%, especially small and medium rated power (1-30 kW motors.

  5. Force per cross-sectional area from molecules to muscles: a general property of biological motors.

    Science.gov (United States)

    Rospars, Jean-Pierre; Meyer-Vernet, Nicole

    2016-07-01

    We propose to formally extend the notion of specific tension, i.e. force per cross-sectional area-classically used for muscles, to quantify forces in molecular motors exerting various biological functions. In doing so, we review and compare the maximum tensions exerted by about 265 biological motors operated by about 150 species of different taxonomic groups. The motors considered range from single molecules and motile appendages of microorganisms to whole muscles of large animals. We show that specific tensions exerted by molecular and non-molecular motors follow similar statistical distributions, with in particular, similar medians and (logarithmic) means. Over the 10(19) mass (M) range of the cell or body from which the motors are extracted, their specific tensions vary as M(α) with α not significantly different from zero. The typical specific tension found in most motors is about 200 kPa, which generalizes to individual molecular motors and microorganisms a classical property of macroscopic muscles. We propose a basic order-of-magnitude interpretation of this result.

  6. Sport expert's motor imagery: functional imaging of professional motor skills and simple motor skills.

    Science.gov (United States)

    Wei, Gaoxia; Luo, Jing

    2010-06-23

    Numerous studies provide evidence that motor skill acquisition is associated with dynamic changes in cortical and subcortical regions. Athletes are a professional population who are engaged in extensive motor training for long periods. However, the neural substrates of extreme level motor performance have not been clarified. We used kinesthetic imagery task to induce the mental representation of sport expert's extraordinary performance in view of the shared substrates of executing movement and motor imagery. For the first time, we compared, through functional magnetic resonance imaging (fMRI), the pattern of cerebral activations in 12 professional divers and 12 normal people without extensive training, during imagery of professional skills and imagery of simple motor skills. The sport experts showed significant activation in the parahippocampus during imagery of professional skills relative to the novices, which might reflect the representation adapted to experience-related motor tasks. No significant difference was found between experts and novices when they imagined simple motor skills. These results indicated the experts might utilize their kinesthetic imagery more efficiently than novices, but only for the activity in which they had expertise. The sport experts also demonstrated more focused activation patterns in prefrontal areas in both of imagery tasks, which may be relevant to higher order of motor control during motor imagery. Moreover, this study suggested that the brains of sport experts could be regarded as the ideal subjects to explore the relationship between cerebral plasticity and learning of complex motor skills.

  7. Savonius wind motor

    Energy Technology Data Exchange (ETDEWEB)

    Kalopoulos, G.D.

    1993-01-13

    The Savonius motor has a plurality of floor or vertical stages, each floor comprising a pair of semicylindrical blades contained between two parallel horizontal circular discs, the blades being diametrically disposed so that one blade surmounts the other by a lead of 1/8th of their diameter. The bladings in each floor are arranged at a phase difference, so that it becomes possible to exploit even weak winds independent of the direction they blow from and without the wind engine being equipped with a special orientation system. (author)

  8. Control of synchronous motors

    CERN Document Server

    Louis, Jean-Paul

    2013-01-01

    Synchronous motors are indubitably the most effective device to drive industrial production systems and robots with precision and rapidity. Their control law is thus critical for combining at the same time high productivity to reduced energy consummation. As far as possible, the control algorithms must exploit the properties of these actuators. Therefore, this work draws on well adapted models resulting from the Park's transformation, for both the most traditional machines with sinusoidal field distribution and for machines with non-sinusoidal field distribution which are more and more used in

  9. A bottom hole motor

    Energy Technology Data Exchange (ETDEWEB)

    Kibishcher, G.B.; Karpenko, V.K.; Pogorelov, V.P.

    1982-01-01

    A bottom hole motor is proposed which includes a body, a push rod with a piston, a spindle, a mechanism for converting the reciprocal movement of the piston into rotation of the shaft and pump and drain cavities. In order to simplify the design the push rod is made with radial openings above and below the piston, while the shaft is made with two longitudinal channels at the level of the radial openings of the push rod on the diametrically opposite sides. The cavity of one channel is constantly connected with the pump cavity, while the other is permanently connected with the drain cavity.

  10. Motor timing under microgravity.

    Science.gov (United States)

    Semjen, A; Leone, G; Lipshits, M

    1998-01-01

    Five participants were tested on their ability to produce accurate and regular inter-response intervals in the 350 to 530 ms time range. Three of them were members of the French-Russian CASSIOPEE 96 spaceflight mission, and the other two were control subjects tested on the ground. During spaceflight, the target inter-response intervals were increasingly undershot and the timing became more variable (less regular). The increase in the timing variability was mostly attributable to the internal timekeeping processes rather than those involved in motor execution. The results are discussed with reference to the physiological mechanisms possibly underlying the timing of fast serial movements.

  11. Motor cortical plasticity induced by motor learning through mental practice.

    Directory of Open Access Journals (Sweden)

    Laura eAvanzino

    2015-04-01

    Full Text Available Several investigations suggest that actual and mental actions trigger similar neural substrates. Motor learning via physical practice results in long-term potentiation (LTP-like plasticity processes, namely potentiation of M1 and a temporary occlusion of additional LTP-like plasticity. However, whether this neuroplasticity process contributes to improve motor performance through mental practice remains to be determined. Here, we tested skill learning-dependent changes in primary motor cortex (M1 excitability and plasticity by means of transcranial magnetic stimulation in subjects trained to physically execute or mentally perform a sequence of finger opposition movements. Before and after physical practice and motor-imagery practice, M1 excitability was evaluated by measuring the input-output (IO curve of motor evoked potentials. M1 long-term potentiation (LTP and long-term depression (LTD-like plasticity was assessed with paired-associative stimulation (PAS of the median nerve and motor cortex using an interstimulus interval of 25 ms (PAS25 or 10 ms (PAS10, respectively. We found that even if after both practice sessions subjects significantly improved their movement speed, M1 excitability and plasticity were differentially influenced by the two practice sessions. First, we observed an increase in the slope of IO curve after physical but not after motor-imagery practice. Second, there was a reversal of the PAS25 effect from LTP-like plasticity to LTD-like plasticity following physical and motor-imagery practice. Third, LTD-like plasticity (PAS10 protocol increased after physical practice, whilst it was occluded after motor-imagery practice. In conclusion, we demonstrated that motor-imagery practice lead to the development of neuroplasticity, as it affected the PAS25- and PAS10- induced plasticity in M1. These results, expanding the current knowledge on how motor-imagery training shapes M1 plasticity, might have a potential impact in

  12. Noise characteristics of the Escherichia coli rotary motor

    Directory of Open Access Journals (Sweden)

    Clausznitzer Diana

    2011-09-01

    Full Text Available Abstract Background The chemotaxis pathway in the bacterium Escherichia coli allows cells to detect changes in external ligand concentration (e.g. nutrients. The pathway regulates the flagellated rotary motors and hence the cells' swimming behaviour, steering them towards more favourable environments. While the molecular components are well characterised, the motor behaviour measured by tethered cell experiments has been difficult to interpret. Results We study the effects of sensing and signalling noise on the motor behaviour. Specifically, we consider fluctuations stemming from ligand concentration, receptor switching between their signalling states, adaptation, modification of proteins by phosphorylation, and motor switching between its two rotational states. We develop a model which includes all signalling steps in the pathway, and discuss a simplified version, which captures the essential features of the full model. We find that the noise characteristics of the motor contain signatures from all these processes, albeit with varying magnitudes. Conclusions Our analysis allows us to address how cell-to-cell variation affects motor behaviour and the question of optimal pathway design. A similar comprehensive analysis can be applied to other two-component signalling pathways.

  13. Model Studies of the Dynamics of Bacterial Flagellar Motors

    Energy Technology Data Exchange (ETDEWEB)

    Bai, F; Lo, C; Berry, R; Xing, J

    2009-03-19

    The Bacterial Flagellar Motor is a rotary molecular machine that rotates the helical filaments which propel swimming bacteria. Extensive experimental and theoretical studies exist on the structure, assembly, energy input, power generation and switching mechanism of the motor. In our previous paper, we explained the general physics underneath the observed torque-speed curves with a simple two-state Fokker-Planck model. Here we further analyze this model. In this paper we show (1) the model predicts that the two components of the ion motive force can affect the motor dynamics differently, in agreement with the latest experiment by Lo et al.; (2) with explicit consideration of the stator spring, the model also explains the lack of dependence of the zero-load speed on stator number in the proton motor, recently observed by Yuan and Berg; (3) the model reproduces the stepping behavior of the motor even with the existence of the stator springs and predicts the dwelling time distribution. Predicted stepping behavior of motors with two stators is discussed, and we suggest future experimental verification.

  14. Overview of Bearingless Induction Motors

    Directory of Open Access Journals (Sweden)

    Xiaodong Sun

    2014-01-01

    Full Text Available Bearingless induction motors combining functions of both torque generation and noncontact magnetic suspension together have attracted more and more attention in the past decades due to their definite advantages of compactness, simple structure, less maintenance, no wear particles, high rotational speed, and so forth. This paper overviews the key technologies of the bearingless induction motors, with emphasis on motor topologies, mathematical models, and control strategies. Particularly, in the control issues, the vector control, independent control, direct torque control, nonlinear decoupling control, sensorless control, and so forth are investigated. In addition, several possible development trends of the bearingless induction motors are also discussed.

  15. Effect of fuel concentration on cargo transport by a team of Kinesin motors

    Science.gov (United States)

    Takshak, Anjneya; Mishra, Nirvantosh; Kulkarni, Aditi; Kunwar, Ambarish

    2017-02-01

    Eukaryotic cells employ specialized proteins called molecular motors for transporting organelles and vesicles from one location to another in a regulated and directed manner. These molecular motors often work collectively in a team while transporting cargos. Molecular motors use cytoplasmic ATP as fuel, which is hydrolyzed to generate mechanical force. While the effect of ATP concentration on cargo transport by single Kinesin motor function is well understood, it is still unexplored, both theoretically and experimentally, how ATP concentration would affect cargo transport by a team of Kinesin motors. For instance, how does fuel concentration affect the travel distances and travel velocities of cargo? How cooperativity of Kinesin motors engaged on a cargo is affected by ATP concentration? To answer these questions, here we develop mechano-chemical models of cargo transport by a team of Kinesin motors. To develop these models we use experimentally-constrained mechano-chemical model of a single Kinesin motor as well as earlier developed mean-field and stochastic models of load sharing for cargo transport. Thus, our new models for cargo transport by a team of Kinesin motors include fuel concentration explicitly, which was not considered in earlier models. We make several interesting predictions which can be tested experimentally. For instance, the travel distances of cargos are very large at limited ATP concentrations in spite of very small travel velocity. Velocities of cargos driven by multiple Kinesin have a Michaelis-Menten dependence on ATP concentration. Similarly, cooperativity among the engaged Kinesin motors on the cargo shows a Michaelis-Menten type dependence, which attains a maximum value near physiological ATP concentrations. Our new results can be potentially useful in controlling artificial nano-molecular shuttles precisely for targeted delivery in various nano-technological applications.

  16. Modeling neck linker of kinesin motor movement with MRSR stochastic differential equation

    Science.gov (United States)

    Razali, Wan Qashishah Akmal Wan; Ramli, Siti Norafidah Mohd; Radiman, Shahidan

    2016-11-01

    Stochastic differential equation has a significant role in a range of biological areas including molecular motor like kinesin motor. Mean-reverting square root (MRSR) stochastic differential equation is commonly used in economics and finance areas. In this study, we use the MRSR stochastic differential equation to model neck linker motion of kinesin motor by considering the possibilities of rightward direction and occasionally in the leftward direction of kinesin movements. This neck linker docking model of kinesin motor incorporates the conformational change in the chemical kinetics and the tethered diffusion of the free head of kinesin motor. Here, we demonstrate this model by using Hookean spring method which referred to the stiffness model of neck linker. The motion of kinesin motor seems to be well described to move in unidirectional way with volatile behavior based on MRSR rather than common stochastic differential equation [DOI 10.1007/s11538-011-9697-6].

  17. A stochastic model for microtubule motors describes the in vivo cytoplasmic transport of human adenovirus.

    Directory of Open Access Journals (Sweden)

    Mattia Gazzola

    2009-12-01

    Full Text Available Cytoplasmic transport of organelles, nucleic acids and proteins on microtubules is usually bidirectional with dynein and kinesin motors mediating the delivery of cargoes in the cytoplasm. Here we combine live cell microscopy, single virus tracking and trajectory segmentation to systematically identify the parameters of a stochastic computational model of cargo transport by molecular motors on microtubules. The model parameters are identified using an evolutionary optimization algorithm to minimize the Kullback-Leibler divergence between the in silico and the in vivo run length and velocity distributions of the viruses on microtubules. The present stochastic model suggests that bidirectional transport of human adenoviruses can be explained without explicit motor coordination. The model enables the prediction of the number of motors active on the viral cargo during microtubule-dependent motions as well as the number of motor binding sites, with the protein hexon as the binding site for the motors.

  18. A stochastic model for microtubule motors describes the in vivo cytoplasmic transport of human adenovirus.

    Science.gov (United States)

    Gazzola, Mattia; Burckhardt, Christoph J; Bayati, Basil; Engelke, Martin; Greber, Urs F; Koumoutsakos, Petros

    2009-12-01

    Cytoplasmic transport of organelles, nucleic acids and proteins on microtubules is usually bidirectional with dynein and kinesin motors mediating the delivery of cargoes in the cytoplasm. Here we combine live cell microscopy, single virus tracking and trajectory segmentation to systematically identify the parameters of a stochastic computational model of cargo transport by molecular motors on microtubules. The model parameters are identified using an evolutionary optimization algorithm to minimize the Kullback-Leibler divergence between the in silico and the in vivo run length and velocity distributions of the viruses on microtubules. The present stochastic model suggests that bidirectional transport of human adenoviruses can be explained without explicit motor coordination. The model enables the prediction of the number of motors active on the viral cargo during microtubule-dependent motions as well as the number of motor binding sites, with the protein hexon as the binding site for the motors.

  19. Catch-slip bonds can be dispensable for motor force regulation during skeletal muscle contraction

    Science.gov (United States)

    Dong, Chenling; Chen, Bin

    2015-07-01

    It is intriguing how multiple molecular motors can perform coordinated and synchronous functions, which is essential in various cellular processes. Recent studies on skeletal muscle might have shed light on this issue, where rather precise motor force regulation was partly attributed to the specific stochastic features of a single attached myosin motor. Though attached motors can randomly detach from actin filaments either through an adenosine triphosphate (ATP) hydrolysis cycle or through "catch-slip bond" breaking, their respective contribution in motor force regulation has not been clarified. Here, through simulating a mechanical model of sarcomere with a coupled Monte Carlo method and finite element method, we find that the stochastic features of an ATP hydrolysis cycle can be sufficient while those of catch-slip bonds can be dispensable for motor force regulation.

  20. Experimental demonstration of a single-molecule electric motor.

    Science.gov (United States)

    Tierney, Heather L; Murphy, Colin J; Jewell, April D; Baber, Ashleigh E; Iski, Erin V; Khodaverdian, Harout Y; McGuire, Allister F; Klebanov, Nikolai; Sykes, E Charles H

    2011-09-04

    For molecules to be used as components in molecular machines, methods that couple individual molecules to external energy sources and that selectively excite motion in a given direction are required. Significant progress has been made in the construction of molecular motors powered by light and by chemical reactions, but electrically driven motors have not yet been built, despite several theoretical proposals for such motors. Here we report that a butyl methyl sulphide molecule adsorbed on a copper surface can be operated as a single-molecule electric motor. Electrons from a scanning tunnelling microscope are used to drive the directional motion of the molecule in a two-terminal setup. Moreover, the temperature and electron flux can be adjusted to allow each rotational event to be monitored at the molecular scale in real time. The direction and rate of the rotation are related to the chiralities of both the molecule and the tip of the microscope (which serves as the electrode), illustrating the importance of the symmetry of the metal contacts in atomic-scale electrical devices.