Modelling Cell Orientation Under Stretch: The Effect of Substrate Elasticity.

When cells are seeded on a cyclically deformed substrate like silicon, they tend to reorient their major axis in two ways: either perpendicular to the main stretching direction, or forming an oblique angle with it. However, when the substrate is very soft such as a collagen gel, the oblique orientation is no longer observed, and the cells align either along the stretching direction, or perpendicularly to it. To explain this switch, we propose a simplified model of the cell, consisting of two elastic elements representing the stress fiber/focal adhesion complexes in the main and transverse directions. These elements are connected by a torsional spring that mimics the effect of crosslinking molecules among the stress fibers, which resist shear forces. Our model, consistent with experimental observations, predicts that there is a switch in the asymptotic behaviour of the orientation of the cell determined by the stiffness of the substratum, related to a change from a supercritical bifurcation scenario, whereby the oblique configuration is stable for a sufficiently large stiffness, to a subcritical bifurcation scenario at a lower stiffness. Furthermore, we investigate the effect of cell elongation and find that the region of the parameter space leading to an oblique orientation decreases as the cell becomes more elongated. This implies that elongated cells, such as fibroblasts and smooth muscle cells, are more likely to maintain an oblique orientation with respect to the main stretching direction. Conversely, rounder cells, such as those of epithelial or endothelial origin, are more likely to switch to a perpendicular or parallel orientation on soft substrates.