Multi-level molecular clutches in motile cell processes.

To trigger cell motility, forces generated by the cytoskeleton must be transmitted physically to the external environment through transmembrane adhesion molecules. One model put forward twenty years ago to describe this process is the molecular clutch by which a modular interface of adaptor proteins mediates a dynamic mechanical connection between the actin flow and cell adhesion complexes. Recent optical imaging experiments have identified key clutch molecules linked to specific chemical and mechanical signal transduction pathways, particularly regarding integrins in migrating cells, IgCAMs in neuronal growth cones, and cadherins at intercellular junctions. We propose here the concept of a multi-level clutch as a useful analogy to grasp the complexity of the dynamic molecular interactions involved in a panel of motile behaviors and shapes.