This research is intended to elucidate the mechanism by which force is developed by the interaction of myosin and actin molecules in muscle (and in a number of other motile systems) and will focus on the dynamics of the changes taking place in the crossbridges in striated muscle during contraction. It has long been established that muscle contraction is brought about by a sliding filament mechanism, in which partially overlapping arrays of actin and myosin filaments are acted on by a relative sliding force which leads to shortening of the muscle. It is generally believed that this force is generated by a cyclic interaction of myosin crossbridges with sites on the actin filaments. However, the structural details of the process have proved to be particularly difficult to establish, partly because of the transient and unsynchronized nature of many of the changes taking place, and partly because of the technical difficulty of obtaining submicroscopic structural information about any rapidly changing biological system. The development of rapid freezing techniques by Heuser and others has now made it possible in principle to obtain electron microscope images of these transient structural states and suitable variations of these techniques will be developed to enable correlations to be made with evidence derived from time-resolved x-ray diffraction studies. These approaches should provide important new information about the structural behavior of the crossbridges as they interact with actin and develop force. When combined with new information from biochemical and physiological studies, the results of the present work should materially advance our understanding of this very fundamental biological mechanism.
