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- W3004740921 abstract "Molecular measurements of actomyosin are well-described by a four-state mechanochemical model, with two states where myosin is bound to actin and two states where myosin and actin do not interact. Biochemical measurements, however, show a weakly-bound interaction between actin and myosin that is too brief to observe with the standard time resolution of molecular experiments. To understand the effect of a weakly-bound interaction, we quantitatively compared the predictions of two mathematical models, 1) a four-state model (lacking a weakly-bound state), and 2) a five-state model (including a weakly-bound state), to muscle fiber measurements. Both models fit classic measurements of heat generation as a function of work (the Fenn effect) and the force-velocity relationship. But only the five-state model, incorporating weak binding, fits both measurements using the same parameters. Further, weak binding is necessary to reproduce the immediate peak in force and subsequent decay that occurs after a muscle fiber is rapidly stretched a small distance (phase I and II in the tension transient). In the model, weakly-bound cross-bridges effectively act as a viscous drag on the thin filament. However, if myosin is linearly elastic, the model is unable to simultaneously fit force-velocity and tension transient measurements from the same muscle fiber. These data suggest different amounts of weak-binding, with tension transients requiring more, and force-velocity requiring less. Nonlinear cross-bridge elasticity resolves this problem, since buckling of compressed myosin molecules decreases the stiffness of only negatively strained myosin, thereby decreasing viscous drag from weakly-bound cross-bridges during muscle shortening (as in the force-velocity), while minimally effecting viscous drag during muscle lengthening (as in tension transients after stretch)." @default.
- W3004740921 created "2020-02-14" @default.
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- W3004740921 date "2020-02-01" @default.
- W3004740921 modified "2023-10-01" @default.
- W3004740921 title "Weakly-Bound, Non-Linear Elastic Cross-Bridges are Required to Self-Consistently Model the FENN Effect, Force Velocity and Tension Transients in Muscle Fibers" @default.
- W3004740921 doi "https://doi.org/10.1016/j.bpj.2019.11.2741" @default.
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