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. 1998 Dec;75(6):2996–3007. doi: 10.1016/S0006-3495(98)77740-9

Direct tests of muscle cross-bridge theories: predictions of a Brownian dumbbell model for position-dependent cross-bridge lifetimes and step sizes with an optically trapped actin filament.

D A Smith 1
PMCID: PMC1299970  PMID: 9826619

Abstract

Force and displacement events from a single myosin molecule interacting with an actin filament suspended between optically trapped beads (Finer, J. T., R. M. Simmons, and J. A. Spudich. 1994. Nature. 368:113-119) can be interpreted in terms of a generalized cross-bridge model that includes the effects of Brownian forces on the beads. Steady-state distributions of force and displacement can be obtained directly from a generalized Smoluchowski equation for Brownian motion of the actin-bead "dumbbell," and time series from Monte Carlo simulations of the corresponding Langevin equation. When the frequency spectrum of Brownian motion extends beyond cross-bridge transition rates, the inverse mean lifetimes of force/displacement pulses are given by cross-bridge rate constants averaged over a Boltzmann distribution of Brownian noise. These averaged rate constants reflect the strain-dependence of the rate constants for the stationary filament, most faithfully at high trap stiffness. Hence, measurements of the lifetimes and displacements of single events as a function of the resting position of the dumbbell can provide a direct test of different cross-bridge theories of muscle contraction. Quantitative demonstrations are given for Huxley models with 1) faster binding or 2) slower dissociation at positive cross-bridge strain. Predictions for other models can be inferred from the averaging procedure.

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