Muscle Contraction Mechanisms by Use of Synchrotron X‐Ray Diffraction/Scattering: Coordinated Changes of Actin and Myosin

Abstract

Muscle contraction occurs when the main constitutive proteins, actin and myosin interact via crossbridge formation, powered by the hydrolysis of ATP. It is a physical process that transduces chemical energy into mechanical work, producing directional motion. The central question is how force generation and movement in muscle contraction are associated with conformational changes in contractile and regulatory proteins. The best available technique for such an approach is X‐ray diffraction which provides in situ structural information with a submolecular resolution. X‐ray diffraction/scattering with intense synchrotron radiation has demonstrated a structural basis for the molecular mechanism underlying muscle contraction with high spatial‐ and time‐resolution. The structural changes in skeletal muscles undergoing contraction by synchrotron X‐ray diffraction are outlined by putting weight on the thin actin filament as the locus of actomyosin interaction and regulation. Evidence is provided that actin filament is not a passive scaffold on which myosin heads rotate, but has an active mechanochemical role in muscle contraction. Key Concepts Muscle contraction occurs when constitutive proteins actin and myosin in muscle interact with each other, powered by the hydrolysis of adenosine triphosphate (ATP), leading to a force generation or a shortening of the sarcomere. Sliding filament theory was a proposal on the basis of the discovery that when a sarcomere shortens, two types of filaments slide past each other with little change in their lengths, resulting in an overall shortening of muscle. Elastic elements sustaining the tension that muscle exerts during contraction are thought to be resided somewhere in the sarcomere. In the current hypothesis, the only elastic elements have been assumed to reside certain places around or within the myosin heads interacting with actin filaments. The force is transmitted to the ends of the contractile unit through the thin actin filaments, which have been thought to contribute very little compliance to the mechanochemical machinery. Evidence that the thin actin filaments and thick myosin filaments, too are purely elastic under active force generation has been obtained. Extensibility accompanies twisting changes in both filaments. Twisting of the actin filament suggests that the force acting at an actomyosin crossbridge contains torque components around the axis of the actin filament. X‐ray diffraction/scattering is the interference of the X‐rays scattered from the electron densities of the matter, and Fourier transformation of the interference pattern yields the structure of the matter. Synchrotron radiations are electromagnetic waves that are emitted in the tangential direction of the orbit when electrons or positrons are circulating near the speed of light in an accelerating ring (synchrotron). Synchrotron radiation X‐rays with high brilliance and collimation are an indispensable tool for muscle structural research.