Analysis and interpretation of stress fiber organization in cells subject to cyclic stretch

Numerical simulations that incorporate a biochemomechanical 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 contraction of the substrate. Conversely, equibiaxial cyclic stretching induces a uniform distribution of stress fiber orientations. Demonstrations that the model successfully predicts the alignments experimentally found are followed by a parameter study to investigate the influence of a range of key variables including the stretch magnitude, the intrinsic rate sensitivity of the stress fibers, the straining frequency, and the transverse contraction of the substrate. The primary predictions are as follows. The rate sensitivity has a strong influence on alignment, equivalent to that attained by a few percent of additional stretch. 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.