Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions.

Integrins are transmembrane receptors that, upon activation, bind extracellular matrix (ECM) or cell surface ligands and link them to the actin cytoskeleton to mediate cell adhesion and migration1,2. One model for the structural transitions mediating integrin activation termed \"the cytoskeletal force hypothesis\" posits that force transmitted from the cytoskeleton to ligand-bound integrins acts as an allosteric stabilizer of the extended-open, high-affinity state3. Since cytoskeletal forces in migrating cells are generated by centripetal \"retrograde flow\" of F-actin from the cell leading edge, where integrin-based adhesions are initiated4,5, this model predicts that F-actin flow should al