The Role of the Scar/WAVE Complex in the Mechanics of Cell Migration

Abstract

Cell motility is integral to a wide spectrum of biological phenomena. It requires the spatiotemporal coordination of underlying biochemical processes, resulting in cyclic shape changes associated with mechanical events (the motility cycle). A major driving force of cell migration is the dendritic polymerization of actin at the leading edge, regulated through the nucleation activity of the Arp2/3 complex, activated by the Scar/WAVE complex. Our aim is to understand the effect of the different components of the Scar/WAVE complex in the mechanics and in particular the motility cycle of migrating cells. For this purpose, we acquired time-lapse recordings of cell shape and traction forces of Dictyostelium cells migrating on deformable substrates. We compared results for wild-type cells and cells lacking the Scar/WAVE complex proteins PIR121 (Sra-1/CYFIP/GEX-2) (pirA-) and SCAR (scrA-). We find that mutantcells move slower than wild-type, while maintaining the overall characteristics of the mechanical interaction with the substrate, attaching at front and back and contracting inwards. Although the distribution of applied forces is unchanged, their magnitude is lower than in wild-type for scrA- cells and higher for pirA- cells. This correlates with the F-actin content of the different cell lines corroborating a role for F-actin in determining the level of the traction stresses. In pirA- cells regularity of the motility cycle (quasiperiodic repetition of shape changes and strain energy deposited) seems to be reduced compared to wild-type. This suggests that proper regulation of the Scar/WAVE complex and its role in F-actin turnover is essential for amoeboid motility.