Past, present and future experiments on muscle

Since the basic outline of the sliding filament mechanism became apparent s ome 45 years ago, the principal challenge, an experimental one, has been to produce definitive evidence about the detailed molecular mechanisms by whi ch myosin cross-bridges produce force and movement in a muscle. More recent ly, similar questions could be Dosed about other molecular motors, in non-m uscle cells. This problem proved unexpectedly difficult to solve, in part b ecause of the technical difficulty of obtaining the structural and mechanic al information required about rapid events within macromolecules, especiall y in a working system, and this triggered many remarkable technical develop ments. There is now very strong evidence for a large change in shape of the myosin heads during ATP hydrolysis, consistent with a lever-arm mechanism. Whether this does indeed provide the driving force for contraction and mov ement-and, if so, exactly how-and whether some other processes could also p lay a significant role, is discussed in the light of the experimental and t heoretical findings presented at this meeting, and other recent and long-te rm evidence.