Unraveling the Role of the SCAR/WAVE Complex in Regulating the Traction Stresses during Amoeboid Motility

Abstract

Chemotaxis, or guided cell migration plays an essential role in many key physiological and disease processes. Chemotaxis requires a tightly regulated, spatiotemporal coordination of underlying biochemical processes. SCAR/WAVE-mediated dendritic F-actin polymerization at the cell's leading edge plays a key role in cell migration. Our study identifies a mechanical and biochemical role for the SCAR/WAVE complex in modulating the traction stresses that drive cell movement. We demonstrate that the traction stresses of wild-type Dictyostelium cells or cells lacking the SCAR/WAVE complex protein PIR121 (pirA-) or SCAR (scrA-) exert stresses of different strength that correlate with their levels of F-actin. By processing the time records of the cell length and the strain energy exerted by the cells on their substrate, we showed that wild-type cells migrate by repeating a specific set of mechanical steps (motility cycle), whereby the cell length (L) and the strain energy exerted by the cells on their substrate (Us) vary periodically. Our analysis also revealed that scrA- cells exhibit an altered motility cycle with a longer period and a lower migration velocity compared to those of wild-type cells. In marked contrast to these strains, pirA-cells, although they have a higher F-actin content, migrate as slowly as scrA- cells but their migration occurs in a seemingly random manner in that they lack the periodic changes in traction stresses that are observed for the other two strains. Finally, by quantifying the level of F-actin in the leading edge in combination with the traction stresses, we demonstrated that the level of leading edge, SCAR/WAVE complex-mediated F-actin polymerizations is critical for the level and spatiotemporal control of the traction stresses, cell-substrate interactions, and the motility cycle.