Abstract
Adaptive force generation of muscle in response to external stimuli is the result of thermally fluctuating, cyclical interactions between myosin and actin, which together form the actomyosin complex. Normally, these fluctuations are modelled using transition rate functions that are based on muscle fiber behaviour, in a phenomenological fashion (Huxley, 1957; Huxley & Simmons, 1971). However, such a basis reduces the predictive power of these models. As an alternative, we propose a model which uses direct single molecule observations of actomyosin fluctuations (Kitamura, et al. Nature 1999, BIOPHYSICS, 2005; Iwaki et al. Nat. Chem Biol. 2009). We precisely estimate the actomyosin potential bias and use diffusion theory to obtain a Brownian ratchet model that reproduces the complete cross-bridge cycle. The model is validated by simulating several macroscopic experimental conditions, while its interpretation is compatible with two different force-generating scenarios (Lorenzo & Yanagida, PloS One, 2012).
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