Annals of Biomedical Engineering

, Volume 36, Issue 10, pp 1624–1640 | Cite as

Towards a Unified Theory of Muscle Contraction. I: Foundations

  • D.A. Smith
  • M.A. Geeves
  • J. Sleep
  • S.M. Mijailovich


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.


Muscle Contraction Lattice Filaments Compliance 



We acknowledge helpful discussions with many people, in particular P. Bennett, K. Burton, M. Irving, P. Luther, A. Mansson, H. Matheiss, G. Offer, V. Ovchinnikov, K.W. Ranatunga, and R.M. Simmons, who have contributed to the evolution of this paper. This work was carried out under a Bioengineering Research Partnership of the National Institutes of Health (Grant no. R01 AR048776). All authors acknowledge financial support from this program. M.A. Geeves is also supported by the Wellcome Trust (Program Grant 07002), and J. Sleep by the Medical Research Council (UK).


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Copyright information

© Biomedical Engineering Society 2008

Authors and Affiliations

  • D.A. Smith
    • 1
    • 2
  • M.A. Geeves
    • 3
  • J. Sleep
    • 4
  • S.M. Mijailovich
    • 5
  1. 1.Department of PhysiologyMonash UniversityClaytonAustralia
  2. 2.Department of ZoologyLatrobe UniversityBundooraAustralia
  3. 3.Department of BiosciencesUniversity of KentCanterburyUK
  4. 4.Randall CentreKing’s College LondonLondonUK
  5. 5.Harvard School of Public HealthBostonUSA

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