Fifty years of muscle and the sliding filament hypothesis.

This review describes the early beginnings of X-ray diffraction work on muscle structure and the contraction mechanism in the MRC Unit in the Cavendish Laboratory, Cambridge, and later work in the MRC Molecular Biology Laboratory in Hills Road, Cambridge, where the author worked for many years, and elsewhere. The work has depended heavily on instrumentation development, for which the MRC laboratory had made excellent provision. The search for ever higher X-ray intensity for time-resolved studies led to the development of synchrotron radiation as an exceptionally powerful X-ray source. This led to the first direct evidence for cross-bridge tilting during force generation in muscle. Further improvements in technology have made it possible to study the fine structure of some of the X-ray reflections from contracting muscle during mechanical transients, and these are currently providing remarkable insights into the detailed mechanism of force development by myosin cross-bridges.