title: On the theory of muscle contraction: filament extensibility and the development of isometric force and stiffness.
abstract: The newly discovered extensibility of actin and myosin filaments challenges the foundation of the theory of muscle mechanics. We have reformulated A. F. Huxley's sliding filament theory to explicitly take into account filament extensibility. During isometric force development, growing cross-bridge tractions transfer loads locally between filaments, causing them to extend and, therefore, to slide locally relative to one another. Even slight filament extensibility implies that 1) relative displacement between the two must be nonuniform along the region of filament overlap, 2) cross-bridge strain must vary systematically along the overlap region, and importantly, 3) the local shortening velocities, even at constant overall sarcomere length, reduce force below the level that would have developed if the filaments had been inextensible. The analysis shows that an extensible filament system with only two states (attached and detached) displays three important characteristics: 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 dissociated from the number of attached cross-bridges 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 coupling occurs exclusively through local sliding velocities, which can be significant, even during isometric force development. The resulting mechanical cooperativity is grounded in fiber mechanics and follows inevitably from filament extensibility.
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts 02115, USA. srbam@ppg-core.harvard.edu
authors.forename: S M
authors.initials: SM
authors.lastname: Mijailovich
authors.forename: J J
authors.initials: JJ
authors.lastname: Fredberg
authors.forename: J P
authors.initials: JP
authors.lastname: Butler
mesh_terms: D000199:Actins / Q000737:chemistry; D000818:Animals; D001696:Biomechanical Phenomena; D055592:Biophysical Phenomena; D001703:Biophysics; D007537:Isometric Contraction / Q000502:physiology*; D008954:Models, Biological; D009218:Myosins / Q000378:metabolism; D012518:Sarcomeres / Q000737:chemistry / Q000502:physiology
chemical_list: D000199:Actins; D009218:Myosins