Towards a Unified Theory of Muscle Contraction. I: Foundations

• Published in: Annals of biomedical engineering Vol. 36; no. 10; pp. 1624 - 1640
• Main Authors: Smith, D.A., Geeves, M.A., Sleep, J., Mijailovich, S.M.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2008; Springer Nature B.V
• Subjects: Actins - physiology; Adenosine Triphosphate - metabolism; Adenosine Triphosphate - physiology; ATP; Biochemistry; Biological and Medical Physics; Biomechanical Phenomena; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Biophysics; Classical Mechanics; Humans; Kinetics; Models, Biological; Muscle Contraction - physiology; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - physiology; Muscle, Striated - metabolism; Muscle, Striated - physiology; Myosins - physiology; Sarcomeres - physiology; Stress, Mechanical; Muscle; Compliance; Filaments; Contraction; Lattice
• ISSN: 0090-6964; 1573-9686; 1573-9686
• DOI: 10.1007/s10439-008-9536-6

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.