Polymer Science applied to the Chemistry of Muscle Movement

All body movement depends on organic chemistry reactions or electrophysical chemistry. Muscle movement is an example.
The first molecular theories, which appeared in the '30's, were based on polymer science. They proposed that there was a rubber-like shortening of myosin filaments brought about by altering the state of ionization of the myosin. This aberration was corrected by the seminal works of HE Huxley (Huxley and Hanson 1954) and AF Huxley (Huxley and Niedergerke 1954) which showed that sarcomeres contained two sets of filaments (thick and thin) which glided over each other without altering their length. Hasselbach showed that the thick filaments contain the protein myosin. The question naturally arose; what made the filaments glide? Projections from the thick filaments, the myosin cross bridges, were discovered by electron microscopy (Huxley 1957; Huxley 1958) and subsequently shown both to be the site of the ATPase and also to be the motor elements producing force and movement between the filaments. Two conformations of the cross-bridge could be detected in insect flight muscle (Reedy et al. 1965). Progress was then rapid so that at a historic Cold Spring Harbor Symposium in 1972 the outline of the molecular mechanism of muscle contraction could be enunciated. The cross bridge was thought to bind to actin in an initial (90°) conformation, go over to a angled (45°) conformation and then release (Huxley 1969) (Lymn and Taylor 1971). For each cycle of activity one ATP would be hydrolyzed. The actual movement could be measured by physiological experiments on contracting muscle and was shown to be about 80-100Å (Huxley and Simmons 1971). Since the cross-bridge was known to be an elongated structure, such a distance could be accommodated by a rotating or swinging cross-bridge model (Fig 2) .

Why did it take so long to work out?

To understand the chemical events which drive muscle one needs to know the protein structures involved at atomic resolution. Muscle is made of massive arrays of macromolecules. How does one get data from such systems? A great deal of technology has been invested in this problem, which has also driven technology. Some early insight was provided by light microscopy. However, the first radical new insight came from electron microscopy. More recently, the structures of the component molecules have been determined x-ray crystallography at atomic resolution. These results now allow us to describe in some detail how the hydrolysis of ATP by the component proteins actin and myosin leads to movement. An understanding of muscle contraction is an important example of the success of protein crystallography, in particular when used in conjunction with high resolution electron microscopy.