A KINETIC MODEL FOR MUSCLE REGULATION

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Studies are proposed to model the transient kinetics of binding the soluble fragments of myosin, S-1 and HMM, to actin and to regulated actin. The role of calcium ions in muscle regulation will also be probed. The primary models to be studied are that of Hill, in which regulated actin may be in either of two states and a new one-state model proposed here, in which cooperativity between bound myosin molecules on a single troponin unit plays a key role. In addition to simple monotonic kinetics, more complex possibilities such as hysteresis and oscillation will be explored. The methods to be employed include analytical and numerical approaches to differential equations as well as Monte Carlo techniques. Extensive comparisons with experimental data will be used to decide among competing models, and the possible effects of using relatively short filaments in in vitro experiments will be considered. Development of a sound model of the kinetics of myosin binding to actin would be a major step toward understanding the functioning and malfunctioning of skeletal muscle regulation.