The aim of this project is to elucidate the molecular mechanism of muscle contraction by following the rotational motion of specific probes attached to myosin cross-bridges in muscle fibers. Muscle fibers will be perturbed chemically or mechanically and the effect of these perturbations on the orientation of the cross-bridges will be followed in the steady state and time-resolved modes. The resulting data will be correlated with the rotating cross-bridge model of muscle contraction. An appealing model of the molecular mechanism of muscle contraction proposes that active protein elements of the mechanism move in a cyclical manner in synchrony with the hydrolysis of ATP to produce muscle shortening against a load. It is known that the head region of myosin (the cross-bridge) contains the hydrolysis site for ATP and acts as a transducer converting chemical energy to mechanical energy. Actin is also of interest in this class of models since the actin filament has specific binding sites for myosin. A popular model of model contraction, the rotating cross-bridge model, serves as a focal point of the experimental investigation of muscle contrating mechanisms by Dr. Burghardt.
