title: Towards a unified theory of muscle contraction. I: foundations.
abstract: Molecular models of contractility in striated muscle require an integrated description of the action of myosin motors, firstly in the filament lattice of the half-sarcomere. Existing models do not adequately reflect the biochemistry of the myosin motor and its sarcomeric environment. The biochemical actin-myosin-ATP cycle is reviewed, and we propose a model cycle with two 4- to 5-nm working strokes, where phosphate is released slowly after the first stroke. A smaller third stroke is associated with ATP-induced detachment from actin. A comprehensive model is defined by applying such a cycle to all myosin-S1 heads in the half-sarcomere, subject to generic constraints as follows: (a) all strain-dependent kinetics required for actin-myosin interactions are derived from reaction-energy landscapes and applied to dimeric myosin, (b) actin-myosin interactions in the half-sarcomere are controlled by matching rules derived from the structure of the filaments, so that each dimer may be associated with a target zone of three actin sites, and (c) the myosin and actin filaments are treated as elastically extensible. Numerical predictions for such a model are presented in the following paper.
authors.affiliation: Department of Physiology, Monash University, Clayton, VIC 3800, Australia. david.smith@med.monash.edu.au
authors.forename: D A
authors.initials: DA
authors.lastname: Smith
authors.forename: M A
authors.initials: MA
authors.lastname: Geeves
authors.forename: J
authors.initials: J
authors.lastname: Sleep
authors.forename: S M
authors.initials: SM
authors.lastname: Mijailovich
mesh_terms: D000199:Actins / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology; D001696:Biomechanical Phenomena; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology*; D054792:Muscle, Striated / Q000378:metabolism / Q000502:physiology; D009218:Myosins / Q000502:physiology; D012518:Sarcomeres / Q000502:physiology; D013314:Stress, Mechanical
chemical_list: D000199:Actins; D000255:Adenosine Triphosphate; D009218:Myosins