Cell migration: Regulation of force on extracellular-matrix-integrin complexes

Cell migration relies upon forces generated by the cell. Recent studies have provided new insights into the processes by which cells generate and regulate the forces applied to extracellular matrix (ECM)-bound integrins and have led us to the working model described here. In this model, ECM binding to integrins in the front of lamellipodia causes those integrins to attach to the rearward-moving cytoskeleton. Integrin-cytoskeleton attachments in the front are strengthened as a result of ECM rigidity, enabling the cell to pull itself forward. The reduction in contact area at the rear compared with that at the lamellipodium concentrates the traction forces in the rear on fewer integrin-ECM bonds, facilitating release. In such a model, cell pathfinding and motility can be influenced by ECM rigidity.