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Assumptions of intrasarcomere symmetry. 


One of the aims of this program is to explore ways in which the structure of the muscle fiber and the sarcomere might be altered by the dynamics of muscle activation. Within the half-sarcomere, it seems plausible to assume that all F-actin filaments in the cross-section of a myofibril bear the same net tension and move in the same way; this would be the case if the temporal behavior of all crossbridges on one myofilament were duplicated on all other myofilaments, which is not likely. Moreover, mirror-like symmetry of the two halves of the sarcomere and the translational symmetry of sarcomeres in series along the fiber are also unlikely to be preserved during contraction. It has been shown that inter-sarcomere symmetry can be disrupted during tetany, leading to force creep or permanent extra tension. We previously modeled the single half-sarcomere under the assumption that intra-sarcomere symmetry is preserved in the mean. The consequences of using a discrete lattice structure, rather than a continuum of head-site spacing, then became evident. Within the region of full filament overlap, net tension on a myofilament can change as a result of variations in the number of heads matched to actin sites as the filaments slide. Sliding occurs when the length of the half-sarcomere changes, or even under isometric conditions as a consequence of the elastic compliance of the filaments. By tuning the parameters of the actomyosin ATPase cycle, most predictions of the model can be brought into qualitative agreement with fiber data. However, in the case of isotonic shortening and ramp stretches, there are discrepancies which are the direct consequence of variable head-site matching. These cases will serve as a test-bed for a more demanding method of computation (Monte-Carlo simulations), in which many filaments in the cross-section of the half-sarcomere are modeled as a single dynamic unit. In this way, the assumption of intra-sarcomere symmetry can be tested. A complete sarcomere and an assembly of sarcomeres in series should ultimately be modeled in the same way and then tested against physiological data. Because the model explicitly predicts spatial position and the state of each myosin head bound to actin, it becomes possible to directly compare predicted integral positions and states of bound myosin heads and X-ray patterns that reveal the dynamic structures of interacting molecules in contracting muscle fibers.

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