TIME-RESOLVED DIFFRACTION STUDIES OF MUSCLE USING SYNCHROTRON-RADIATION

Muscle contraction is one of those biological phenomena that we can al l appreciate in our everyday lives. Sometimes it is when we are restin g quietly and are aware of our heartbeat. At other times it may be whe n we are exerting ourselves and become short of breath, or when we exe rcise for a long period and our muscles start to ache. The way in whic h muscles produce force has exercised the minds of philosophers and sc ientists at least since the days of Erasistratus in the third century BC. Nowadays, of course, we know a very great deal about muscle struct ure, physiology and biochemistry, but we still do not know exactly wha t the molecular process is that produces movement. An ideal way of pro bing this process would be to be able to obtain signals from the relev ant molecules as they actually go through their normal force-generatin g routine in an active muscle. The spatial dimensions involved are in the region of 1-50 nm, thus precluding the use of light microscopy, an d the time regime is microseconds to milliseconds. Techniques with the appropriate spatial resolution might be electron microscopy and x-ray diffraction, but electron microscopy cannot yet be carried out on liv ing tissue. X-ray diffraction methods can clearly have the right sort of spatial resolution, but what about recording diffraction patterns i n the very short times involved (say 1 ms)? It is here that the high f lux from synchrotron storage rings comes into its own. Using synchrotr on radiation from, say, the SRS at the CCLRC Daresbury Laboratory it i s possible to record x-ray diffraction patterns from living muscles in the millisecond time regime and to follow how these diffraction patte rns change as the muscles go through typical contraction cycles. Unfor tunately, x-ray diffraction is not a direct imaging method; the observ ed distribution: of diffracted intensity needs to be interpreted in so me way to give useful information on the spatial relationships of the force-generating molecules. This review details the practical methods involved in recording time-resolved x-ray diffraction patterns from ac tive muscles and the theoretical approaches that are being used to int erpret the diffraction patterns that are obtained. The ultimate aim is to produce a series of time-sliced images of the changing molecular a rrangements and shapes in the muscle as force is produced; together th ese images will form 'Muscle-The Movie'.