Contractile Torque as a Steering Mechanism for Orientation of Adherent Cells

It is well established that adherent cells change their orientation in response to non-uniform substrate stretching. Most observations indicate that cells orient away from the direction of the maximal substrate strain, whereas in some cases cells also align with the direction of the maximal strain. Previous studies suggest that orientation and steering of the cell may be closely tied to cytoskeletal contractile stress but they could not explain the mechanisms that direct cell reorientation. This led us to develop a simple, mechanistic theoretical model that could predict a direction of cell orientation in response to mechanical nonuniformities of the substrate. The model leads to a simple physical mechanism -- namely the contractile torque -- that directs the cell toward a new orientation in response to anisotropic substrate stretching or substrate material anisotropy. A direction of the torque is determined by a dependence of the contractile stress on substrate strain. Model predictions are tested in the case of simple elongation of the substrate and found to be consistent with experimental data from the literature.