ON THE THEORY OF MUSCLE-CONTRACTION - FILAMENT EXTENSIBILITY AND THE DEVELOPMENT OF ISOMETRIC FORCE AND STIFFNESS

The newly discovered extensibility of actin and myosin filaments chall enges the foundation of the theory of muscle mechanics. We have reform ulated A. F. Huxley's sliding filament theory to explicitly take into account filament extensibility. During isometric force development, gr owing cross-bridge tractions transfer loads locally between filaments, causing them to extend and, therefore, to slide locally relative to o ne another. Even slight filament extensibility implies that 1) relativ e displacement between the two must be nonuniform along the region of filament overlap, 2) cross-bridge strain must vary systematically alon g the overlap region, and importantly, 3) the local shortening velocit ies, even at constant overall sarcomere length, reduce force below the level that would have developed if the filaments had been inextensibl e. The analysis shows that an extensible filament system with only two states (attached and detached) displays three important characteristi cs: 1) muscle stiffness leads force during force development; 2) cross -bridge stiffness is significantly higher than previously assessed by inextensible filament models; and 3) stiffness is prominently dissocia ted from the number of attached crossbridges during force development. The analysis also implies that the local behavior of one myosin head must depend on the state of neighboring attachment sites. This couplin g occurs exclusively through local sliding velocities, which can be si gnificant, even during isometric force development. The resulting mech anical cooperativity is grounded in fiber mechanics and follows inevit ably from filament extensibility.