Transient active force generation and stress fibre remodelling in cells under cyclic loading

Abstract

The active cytoskeleton is known to play an important mechanistic role in cellular structure, spreading, and contractility. Contractility is actively generated by stress fibres (SF), which continuously remodel in response to physiological dynamic loading conditions. The influence of actin-myosin cross-bridge cycling on SF remodelling under dynamic loading conditions has not previously been uncovered. In this study, a novel SF cross-bridge cycling model is developed to predict transient active force generation in cells subjected to dynamic loading. Rates of formation of cross-bridges within SFs are governed by the chemical potentials of attached and unattached myosin heads. This transient cross-bridge cycling model is coupled with a thermodynamically motivated framework for SF remodelling to analyse the influence of transient force generation on cytoskeletal evolution. A 1D implementation of the model is shown to correctly predict complex patterns of active cell force generation under a range of dynamic loading conditions, as reported in previous experimental studies.