A cellular automaton model for the regulatory behavior of muscle thin filaments.
Regulation of skeletal muscle contraction is achieved through the interaction of six different proteins: actin, myosin, tropomyosin, and troponins C, I, and T. Many experiments have been performed on the interactions of these proteins, but comparatively less effort has been spent on attempts to integrate the results into a coherent description of the system as a whole. In this paper, we present a new way of approaching the integration problem by using a cellular automaton. We assign rate constants for state changes within each constituent molecule of the muscle thin filament as functions of the states of its neighboring molecules. The automaton shows how the interactions among constituent molecules give rise to the overall regulatory behavior of thin filaments as observed in vitro and is extendable to in vivo measurements. The model is used to predict myosin binding and ATPase activity, and the result is compared with various experimental data. Two important aspects of regulation are revealed by the requirement that the model fit the experimental data: (1) strong interactions must exist between two successively bound myosin heads, and (2) the cooperative binding of calcium to the thin filament can be attributed in a simple way to the interaction between neighboring troponin-tropomyosin units.
Zou
G
G
Department of Computer Science, W.M. Keck Center for Computational Biology, Rice University, Houston, Texas 77251-1892.
Phillips
G N
GN
D008841:Actin Cytoskeleton / Q000502:physiology*; D000199:Actins / Q000737:chemistry / Q000502:physiology; D000818:Animals; D001331:Automation; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D008961:Models, Structural; D009119:Muscle Contraction; D009132:Muscles / Q000502:physiology* / Q000648:ultrastructure; D009218:Myosins / Q000737:chemistry / Q000502:physiology; D014335:Tropomyosin / Q000737:chemistry / Q000502:physiology; D014336:Troponin / Q000737:chemistry / Q000502:physiology
D000199:Actins; D014335:Tropomyosin; D014336:Troponin; D009218:Myosins