title: Actomyosin based contraction: one mechanokinetic model from single molecules to muscle?
abstract: Bridging the gaps between experimental systems on different hierarchical scales is needed to overcome remaining challenges in the understanding of muscle contraction. Here, a mathematical model with well-characterized structural and biochemical actomyosin states is developed to that end. We hypothesize that this model accounts for generation of force and motion from single motor molecules to the large ensembles of muscle. In partial support of this idea, a wide range of contractile phenomena are reproduced without the need to invoke cooperative interactions or ad hoc states/transitions. However, remaining limitations exist, associated with ambiguities in available data for model definition e.g.: (1) the affinity of weakly bound cross-bridges, (2) the characteristics of the cross-bridge elasticity and (3) the exact mechanistic relationship between the force-generating transition and phosphate release in the actomyosin ATPase. Further, the simulated number of attached myosin heads in the in vitro motility assay differs several-fold from duty ratios, (fraction of strongly attached ATPase cycle times) derived in standard analysis. After addressing the mentioned issues the model should be useful in fundamental studies, for engineering of myosin motors as well as for studies of muscle disease and drug development.
authors.affiliation: Department of Chemistry and Biomedical Sciences, Faculty of Health and Life Sciences, Linnaeus University, 39182, Kalmar, Sweden. alf.mansson@lnu.se.
authors.forename: Alf
authors.identifier: 0000-0002-5889-7792
authors.initials: A
authors.lastname: Månsson
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D004548:Elasticity / Q000502:physiology; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D008962:Models, Theoretical; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism
chemical_list: D000205:Actomyosin; D000251:Adenosine Triphosphatases; D009218:Myosins
keywords: Actin; In vitro motility assay; Monte-Carlo simulation; Myosin; Single molecules; Striated muscle