Crawling toward a unified model of cell motility: Spatial and temporal regulation of actin dynamics

Crawling cells of various morphologies displace themselves in their biological environments by a similar overall mechanism of protrusion through actin assembly at the front coordinated with retraction at the rear. Different cell types organize very distinct protruding structures, yet they do so through conserved biochemical mechanisms to regulate actin polymerization dynamics and vary the mechanical properties of these structures. The moving cell must spatially and temporally regulate the biochemical interactions of its protein components to exert control over higher-order dynamic structures created by these proteins and global cellular responses four or more orders of magnitude larger in scale and longer in time than the individual protein-protein interactions that comprise them. To fulfill its biological role, a cell globally responds with high sensitivity to a local perturbation or signal and coordinates its many intracellular actin-based functional structures with the physical environment it experiences to produce directed movement. This review attempts to codify some unifying principles for cell motility that span organizational scales from single protein polymer filaments to whole crawling cells.