Traction Stress Dynamics During Chemotactic Amoeboid Cell Migration

Abstract

Chemotaxis is involved in a broad range of biological phenomena such as during cancer metastasis. It requires a tightly regulated, spatiotemporal coordination of underlying biochemical processes that impact the mechanics of cell migration. In response to intrinsic and environmental cues, motile cells can adapt their migration effectively. Yet both the mechanisms by which this adaptation occurs and the role of the interactions between biochemistry and mechanics of cell migration are largely unknown.We use Fourier Traction Force Microscopy to measure the spatiotemporal evolution of shape and traction stresses and construct traction tension kymographs to analyze cell motility as a function of the dynamics of the cells' mechanically active adhesions (traction adhesions). We show that wild-type cells migrate mainly by forming two stationary traction adhesion sites at their front and back halves, over which the cell body moves forward in a step-wise fashion through periodic axial and, to a lesser degree, lateral contractions. We demonstrate that lateral forces are critical in mediating cell motility and essential for migration on highly adhesive substrates where cells implement two alternate motility modes to achieve migration. Our analysis of two mutant strains that lack distinct F-actin crosslinkers (mhcA- and abp120- cells) also supports a key role for lateral contractions in amoeboid cell motility, while the differences in their traction adhesion dynamics suggest the two mutant strains use distinct mechanisms to achieve migration. The considerable differences we find in both the spatiotemporal organization of traction adhesions and contractility, when comparing to the control wild type, provide insight into the role of the extracellular environment and of key cytoskeletal proteins in cell migration. We propose that these are highly conserved mechanisms, which function in a range of amoeboid cells, including leukocytes, as well as other forms of cell motility.