The position and size of individual focal adhesions are determined by intracellular stress-dependent positive regulation.

It remains unclear how the subcellular positions and sizes of individual focal adhesions (FAs) are determined in stationary cells. The elucidation of spatial regulation mechanisms is important for accurate understanding of the cellular response to mechanical stress. Through a theoretical analysis on previously reported cell behavior, the present study demonstrates a close correlation between the appearances of mechanosensitive elements and intracellular stress reflecting traction stress that the cell exerts on the substrate. The magnitude and distribution of stress were predicted in this analysis by mimicking intrinsic actomyosin contraction independent of extracellular stimuli. Positions of FAs and actin stress fibers corresponded to the local maximum and minimum stress points, respectively, and thus were determined by the global configuration of cell adhesions. Furthermore, their subcellular sizes were in agreement with the predicted stress magnitudes that were dependent on the local mechanical environment. These results suggest that a positive regulation (i.e., force and cell adhesion enhance each other) functions in the organization of individual FAs in nonmigrating cells.