Collective Dynamics of Focal Adhesions Regulate Direction of Cell Motion

Directed cell motion is essential in physiological and pathological processes such as morphogenesis, wound healing, and cancer spreading. Chemotaxis has often been proposed as the driving mechanism, even though evidence of long-range gradients is often lacking in vivo. By patterning adhesive regions in space, we control cell shape and the potential to move along one direction in another migration mode coined ratchetaxis. We report that focal contact distributions collectively dictate cell directionality, and bias is non-linearly increased by gap distance between adhesive regions. Focal contact dynamics on micro-patterns allow to integrate these phenomena in a model where each focal contact is translated into a force with known amplitude and direction, leading to quantitative predictions for cell motion in new conditions with their successful experimental tests. Altogether, our study shows how local and minute timescale dynamics of focal adhesions and their distribution lead to long-term cellular motion with simple geometric rules. A record of this paper's Transparent Peer Review process is included in the Supplemental Information. In this work, Lo Vecchio et al. investigate the interplay between micro-environment geometry, focal adhesion distributions, and net bias in cell migration. Cells are plated on ratchet adhesive motifs separated by tunable gap interdistance. They identify a saturating behavior of focal contact distributions that leads to a non-linear relationship between bias in cell motion and motif interdistance. Simple geometrical arguments on cell and its environment with collective effects of focal adhesions enable to predict quantitatively the net bias in cell motion for new geometries.