The Experts below are selected from a list of 76833 Experts worldwide ranked by ideXlab platform
Hideo Higuchi - One of the best experts on this subject based on the ideXlab platform.
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Coordinated Force Generation of skeletal myosins in myofilaments through motor coupling
Nature Communications, 2017Co-Authors: Motoshi Kaya, Yoshiaki Tani, Takumi Washio, Toshiaki Hisada, Hideo HiguchiAbstract:In contrast to processive molecular motors, skeletal myosins form a large motor ensemble for contraction of muscles against high loads. Despite numerous information on the molecular properties of skeletal myosin, its ensemble effects on collective Force Generation have not been rigorously clarified. Here we show 4 nm stepwise actin displacements generated by synthetic myofilaments beyond a load of 30 pN, implying that steps cannot be driven exclusively by single myosins, but potentially by coordinated Force Generations among multiple myosins. The simulation model shows that stepwise actin displacements are primarily caused by coordinated Force Generation among myosin molecules. Moreover, the probability of coordinated Force Generation can be enhanced against high loads by utilizing three factors: strain-dependent kinetics between Force-generating states; multiple power stroke steps; and high ATP concentrations. Compared with other molecular motors, our findings reveal how the properties of skeletal myosin are tuned to perform cooperative Force Generation for efficient muscle contraction. Skeletal muscle myosin forms large ensembles to generate Force against high loads. Using optical tweezers and simulation Kaya et al . provide experimental evidence for cooperative Force Generation, and describe how the molecular properties of skeletal myosins are tuned for coordinated power strokes.
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Effect of Non-Linear Elasticity of Skeletal Myosins on Force Generation in Muscle
Biophysical Journal, 2012Co-Authors: Motoshi Kaya, Hideo HiguchiAbstract:During muscle Force Generation, an elastic energy stored at the compliant region of myosin head is a source of mechanical work against the external environment. Thus, this elastic distortion of myosin molecule was modeled as an essential mechanical element of the Force Generation driven by the crossbridges (Huxley, 1957). In the crossbridge model, the central assumption of the constant stiffness implies that the negatively-strained myosins must be detached at much higher rate than the positively-strained myosins to avoid the significant drag effect. However, the molecular studies on processive motors, such as kinesin and unconventional myosins, show that the assemblies of these motors do not seem to impede the molecular interactions, although they have much higher duty ratio and thus, a higher chance to cause the molecular interference. Recently, we found that skeletal myosins have the non-linear elasticity, in which stiffness is much higher when they are positively-strained and lower when negatively-strained. Therefore, this non-linear elasticity seems to be the essential and complementary property of motors to avoid the drag Force Generation in the motor assembly. We have currently worked on the theoretical model to investigate the effect of non-linear elasticity on the Force Generation, particularly the Force-velocity relationships and the T1-T2 curves obtained from the muscle fiber quick release experiment.
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Kinetics of Force Generation by single kinesin molecules activated by laser photolysis of caged ATP
Proceedings of the National Academy of Sciences of the United States of America, 1997Co-Authors: Hideo Higuchi, Etsuko Muto, Yuichi Inoue, Toshio YanagidaAbstract:To relate transients of Force by single kinesin molecules with the elementary steps of the ATPase cycle, we measured the time to Force Generation by kinesin after photorelease of ATP from caged ATP. Kinesin-coated beads were trapped by an infrared laser and brought onto microtubules fixed to a coverslip. Tension was applied to a kinesin-microtubule rigor complex using the optical trap, and ATP was released by flash photolysis of caged ATP with a UV laser. Kinesin started to generate Force and move stepwise with a step size of 8 nm at average times of 31, 45, and 79 ms after photorelease of 450, 90, and 18 μM ATP, respectively. The kinetics of Force Generation were consistent with a two-step reaction: ATP binding, with an apparent second-order rate constant of 0.7 μM−1·s−1, followed by Force Generation at 45 s−1 per kinesin molecule. The transient rate of Force Generation was close to the rate of the ATPase cycle in solution, suggesting that the rate-limiting step of ATPase cycle is involved with the Force Generation.
Scott L Delp - One of the best experts on this subject based on the ideXlab platform.
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How muscle fiber lengths and velocities affect muscle Force Generation as humans walk and run at different speeds.
The Journal of experimental biology, 2013Co-Authors: Edith M Arnold, Samuel R Hamner, Ajay Seth, Matthew Millard, Scott L DelpAbstract:The lengths and velocities of muscle fibers have a dramatic effect on muscle Force Generation. It is unknown, however, whether the lengths and velocities of lower limb muscle fibers substantially affect the ability of muscles to generate Force during walking and running. We examined this issue by developing simulations of muscle-tendon dynamics to calculate the lengths and velocities of muscle fibers from electromyographic recordings of 11 lower limb muscles and kinematic measurements of the hip, knee and ankle made as five subjects walked at speeds of 1.0-1.75 m s(-1) and ran at speeds of 2.0-5.0 m s(-1). We analyzed the simulated fiber lengths, fiber velocities and Forces to evaluate the influence of Force-length and Force-velocity properties on Force Generation at different walking and running speeds. The simulations revealed that Force Generation ability (i.e. the Force generated per unit of activation) of eight of the 11 muscles was significantly affected by walking or running speed. Soleus Force Generation ability decreased with increasing walking speed, but the transition from walking to running increased the Force Generation ability by reducing fiber velocities. Our results demonstrate the influence of soleus muscle architecture on the walk-to-run transition and the effects of muscle-tendon compliance on the plantarflexors' ability to generate ankle moment and power. The study presents data that permit lower limb muscles to be studied in unprecedented detail by relating muscle fiber dynamics and Force Generation to the mechanical demands of walking and running.
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How muscle fiber lengths and velocities affect muscle Force Generation as humans walk and run at different speeds
Journal of Experimental Biology, 2013Co-Authors: Edith M Arnold, Ajay Seth, Matthew Millard, Samuel Hamner, Scott L DelpAbstract:Summary The lengths and velocities of muscle fibers have a dramatic effect on muscle Force Generation. It is unknown, however, whether the lengths and velocities of lower limb muscle fibers substantially affect the ability of muscles to generate Force during walking and running. We examined this issue by developing simulations of muscle-tendon dynamics that calculate the lengths and velocities of muscle fibers from electromyographic recordings of eleven lower limb muscles and kinematic measurements of the hip, knee, and ankle made as five subjects walked at speeds of 1.0-1.75 m/s and ran at speeds of 2.0-5.0 m/s. We analyzed the simulated fiber lengths, fiber velocities, and Forces to evaluate the influence of Force-length and Force-velocity properties on Force Generation at different walking and running speeds. The simulations revealed that Force Generation ability (i.e., the Force generated per unit of activation) of eight of the eleven muscles was significantly affected by walking or running speed. Soleus Force Generation ability decreased with increasing walking speed, but the transition from walking to running increased the Force Generation ability by reducing fiber velocities. Our results demonstrate the influence of soleus muscle architecture on the walk-to-run transition and the effects of muscle-tendon compliance on the plantarflexors9 ability to generate ankle moment and power. The study presents data that permit lower limb muscles to be studied in unprecedented detail by relating muscle fiber dynamics and Force Generation to the mechanical demands of walking and running.
Toshio Yanagida - One of the best experts on this subject based on the ideXlab platform.
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Direct visualization of human myosin II Force Generation using DNA origami-based thick filaments
Communications Biology, 2019Co-Authors: Keisuke Fujita, Masashi Ohmachi, Keigo Ikezaki, Toshio Yanagida, Mitsuhiro IwakiAbstract:The sarcomere, the minimal mechanical unit of muscle, is composed of myosins, which self-assemble into thick filaments that interact with actin-based thin filaments in a highly-structured lattice. This complex imposes a geometric restriction on myosin in Force Generation. However, how single myosins generate Force within the restriction remains elusive and conventional synthetic filaments do not recapitulate the symmetric bipolar filaments in sarcomeres. Here we engineered thick filaments using DNA origami that incorporate human muscle myosin to directly visualize the motion of the heads during Force Generation in a restricted space. We found that when the head diffuses, it weakly interacts with actin filaments and then strongly binds preferentially to the forward region as a Brownian ratchet. Upon strong binding, the two-step lever-arm swing dominantly halts at the first step and occasionally reverses direction. Our results illustrate the usefulness of our DNA origami-based assay system to dissect the mechanistic details of motor proteins.Fujita, Ochmachi et al combine a DNA origami approach with darkfield microscopy and AFM to study conformational changes in muscle myosin. They generate DNA origami-based thick filaments that enable the direct visualisation of mechanistic details of myosins during Force Generation under geometric conditions that resemble those in muscle.
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direct visualization of human myosin ii Force Generation using dna origami based thick filaments
bioRxiv, 2019Co-Authors: Keisuke Fujita, Masashi Ohmachi, Keigo Ikezaki, Toshio Yanagida, Mitsuhiro IwakiAbstract:Abstract Muscle contraction can be explained by the swinging lever-arm model. However, the dynamic features of how the myosin head swings the lever-arm and its initial interactions with actin are not well understood even though they are essential for the muscle Force Generation, contraction speed, heat production, and response to mechanical perturbations. This is because myosin heads during Force Generation have not been directly visualized. Here, we engineered thick filaments composed of DNA origami and recombinant human muscle myosin, and directly visualized the heads during Force Generation using nanometer-precision single-molecule imaging. We found that when the head diffuses, it weakly interacts with actin filaments and then strongly binds preferentially to the forward region as a Brownian ratchet. Upon strong binding, the head two-step lever-arm swing dominantly halts at the first step and occasionally reverses direction. These results can explain all mechanical characteristics of muscle contraction and suggest that our DNA origami-based assay system can be used to dissect the mechanistic details of motor proteins.
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Kinetics of Force Generation by single kinesin molecules activated by laser photolysis of caged ATP
Proceedings of the National Academy of Sciences of the United States of America, 1997Co-Authors: Hideo Higuchi, Etsuko Muto, Yuichi Inoue, Toshio YanagidaAbstract:To relate transients of Force by single kinesin molecules with the elementary steps of the ATPase cycle, we measured the time to Force Generation by kinesin after photorelease of ATP from caged ATP. Kinesin-coated beads were trapped by an infrared laser and brought onto microtubules fixed to a coverslip. Tension was applied to a kinesin-microtubule rigor complex using the optical trap, and ATP was released by flash photolysis of caged ATP with a UV laser. Kinesin started to generate Force and move stepwise with a step size of 8 nm at average times of 31, 45, and 79 ms after photorelease of 450, 90, and 18 μM ATP, respectively. The kinetics of Force Generation were consistent with a two-step reaction: ATP binding, with an apparent second-order rate constant of 0.7 μM−1·s−1, followed by Force Generation at 45 s−1 per kinesin molecule. The transient rate of Force Generation was close to the rate of the ATPase cycle in solution, suggesting that the rate-limiting step of ATPase cycle is involved with the Force Generation.
Edith M Arnold - One of the best experts on this subject based on the ideXlab platform.
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How muscle fiber lengths and velocities affect muscle Force Generation as humans walk and run at different speeds.
The Journal of experimental biology, 2013Co-Authors: Edith M Arnold, Samuel R Hamner, Ajay Seth, Matthew Millard, Scott L DelpAbstract:The lengths and velocities of muscle fibers have a dramatic effect on muscle Force Generation. It is unknown, however, whether the lengths and velocities of lower limb muscle fibers substantially affect the ability of muscles to generate Force during walking and running. We examined this issue by developing simulations of muscle-tendon dynamics to calculate the lengths and velocities of muscle fibers from electromyographic recordings of 11 lower limb muscles and kinematic measurements of the hip, knee and ankle made as five subjects walked at speeds of 1.0-1.75 m s(-1) and ran at speeds of 2.0-5.0 m s(-1). We analyzed the simulated fiber lengths, fiber velocities and Forces to evaluate the influence of Force-length and Force-velocity properties on Force Generation at different walking and running speeds. The simulations revealed that Force Generation ability (i.e. the Force generated per unit of activation) of eight of the 11 muscles was significantly affected by walking or running speed. Soleus Force Generation ability decreased with increasing walking speed, but the transition from walking to running increased the Force Generation ability by reducing fiber velocities. Our results demonstrate the influence of soleus muscle architecture on the walk-to-run transition and the effects of muscle-tendon compliance on the plantarflexors' ability to generate ankle moment and power. The study presents data that permit lower limb muscles to be studied in unprecedented detail by relating muscle fiber dynamics and Force Generation to the mechanical demands of walking and running.
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How muscle fiber lengths and velocities affect muscle Force Generation as humans walk and run at different speeds
Journal of Experimental Biology, 2013Co-Authors: Edith M Arnold, Ajay Seth, Matthew Millard, Samuel Hamner, Scott L DelpAbstract:Summary The lengths and velocities of muscle fibers have a dramatic effect on muscle Force Generation. It is unknown, however, whether the lengths and velocities of lower limb muscle fibers substantially affect the ability of muscles to generate Force during walking and running. We examined this issue by developing simulations of muscle-tendon dynamics that calculate the lengths and velocities of muscle fibers from electromyographic recordings of eleven lower limb muscles and kinematic measurements of the hip, knee, and ankle made as five subjects walked at speeds of 1.0-1.75 m/s and ran at speeds of 2.0-5.0 m/s. We analyzed the simulated fiber lengths, fiber velocities, and Forces to evaluate the influence of Force-length and Force-velocity properties on Force Generation at different walking and running speeds. The simulations revealed that Force Generation ability (i.e., the Force generated per unit of activation) of eight of the eleven muscles was significantly affected by walking or running speed. Soleus Force Generation ability decreased with increasing walking speed, but the transition from walking to running increased the Force Generation ability by reducing fiber velocities. Our results demonstrate the influence of soleus muscle architecture on the walk-to-run transition and the effects of muscle-tendon compliance on the plantarflexors9 ability to generate ankle moment and power. The study presents data that permit lower limb muscles to be studied in unprecedented detail by relating muscle fiber dynamics and Force Generation to the mechanical demands of walking and running.
Sean X. Sun - One of the best experts on this subject based on the ideXlab platform.
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Dynamics of myosin-driven skeletal muscle contraction: I. Steady-state Force Generation.
Biophysical journal, 2005Co-Authors: Ganhui Lan, Sean X. SunAbstract:Skeletal muscle contraction is a canonical example of motor-driven Force Generation. Despite the long history of research in this topic, a mechanistic explanation of the collective myosin Force Generation is lacking. We present a theoretical model of muscle contraction based on the conformational movements of individual myosins and experimentally measured chemical rate constants. Detailed mechanics of the myosin motor and the geometry of the sarcomere are taken into account. Two possible scenarios of Force Generation are examined. We find only one of the scenarios can give rise to a plausible contraction mechanism. We propose that the synchrony in muscle contraction is due to a Force-dependent ADP release step. Computational results of a half sarcomere with 150 myosin heads can explain the experimentally measured Force-velocity relationship and efficiency data. We predict that the number of working myosin motors increases as the load Force is increased, thus showing synchrony among myosin motors during muscle contraction. We also find that titin molecules anchoring the thick filament are passive Force generators in assisting muscle contraction.
