Numerical simulations that incorporate a bio-chemo-mechanical model for the contractility of the cytoskeleton have been used to rationalize the following observations. Uniaxial cyclic stretching of cells causes stress fibers to align perpendicular to the stretch direction, with degree of alignment dependent on the stretch strain magnitude, as well as the frequency and the transverse strain. Conversely, equibiaxial cyclic stretching induces a uniform distribution of stress fiber orientations. Demonstrations that the model successfully predicts the alignments found experimentally are followed by a parameter study to investigate the influence of the straining frequency and the transverse contraction of the substrate. The primary predictions are as follows. The fiber alignment increases with increasing cycling frequency. Transverse contraction of the substrate causes the stress fibers to organize into two symmetrical orientations with respect to the primary stretch direction.

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