Stress-dependent formation of focal adhesions.

Three-dimensional reconstruction of confocal images of fibroblasts on large rectangular micropatterned substrates shows that stress fibers are connected to the mature focal adhesion sites at the two ends along the long axis of the cell (Fig. 2B). Through these focal adhesions, mechanical forces can be transmitted from the cytoskeleton to the substrate, and vice versa. The formation and maturation of these focal adhesion complexes in cells are known to be tension-dependent (52). To capture the tension-dependent formation of the focal adhesions, we use a continuum model that treats the adhesion layer shown in SI Appendix, Fig. S4C as a set of initially soft nonlinear mechanical elements (SI Appendix, Fig. S4A) that stiffen with tension (SI Appendix, Fig. S4B). As shown in SI Appendix, Fig. S4D, when the tensile stress exerted by the cell to the adhesion layer exceeds a certain threshold, mature focal adhesions are formed, and the cell is connected to the substrate. Below this threshold, the stiffness of the adhesion layer remains low and the substrate experiences negligible forces.