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Dynamics of Myosin-Driven Skeletal Muscle Contraction: I. Steady-State Force Generation

Ganhui Lan ^* and Sean X. Sun ^* 

^* Department of Mechanical Engineering, and Whitaker Institute of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland

Correspondence: Address reprint requests to S. X. Sun, Tel.: 410-516-4003; E-mail: ssun{at}jhu.edu.

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.

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