Materials Science & Engineering

Biography

Biography: Haruo Sugi

Abstract

Molecular mechanism of muscle contraction has been studied intensively over more than 50 years, since the monumental discovery that muscle contraction results from relative sliding between actin and myosin filaments coupled with ATP hydrolysis. It is generally believed that myosin heads (M) extending from myosin filaments first attach to actin in the form of M・ADP・Pi, perform power stroke producing myofilament sliding coupled with release of Pi and ADP, and then detach from actin when next ATP comes to bind it to form M・ATP. Myosin heads detached from actin perform recovery stroke coupled with reaction M・ATP → M・ADP・Pi, and again attach to actin. The amplitude of myosin head power and recovery strokes still remains to be a matter for debate and speculation. As early as late 1980s, we started to visualize ATP-induced myosin head movement in hydrated myosin filaments electron microscopically by using a carbon film-sealed liquid cell. We used synthetic myosin filaments, in which individual myosin heads were position-marked with colloidal gold particles and monoclonal antibodies to myosin head. Filaments were observed under a magnification of 10,000X, and their images were recorded with an imaging plate system. Care was taken to limit total incident electron dose below the value to impair function of muscle proteins. The results obtained are summarized as follows: (1) muscle myofilament sample attach firmly to carbon sealing film; (2) time averaged mean position of individual myosin heads do not change appreciably with time; (3) in the absence of actin filaments, myosin heads move in response to ATP by ~6nm away from the center of myosin filaments, indicating that myosin head recovery stroke takes place without being guided by actin filaments; (4) in the presence of actin filaments, myosin heads perform power stroke in response to ATP with amplitudes depending on experimental conditions.