Molecules, Mechanics, and Migration of Cells

Abstract

A mechanistic model for migration of mammalian blood and tissue cells over two-dimensional substrata has been developed in order to understand effects of interactions of cell surface adhesion receptors with extracellular matrix ligands and intracellular cytoskeletal components. A central prediction of the model — that cell migration speed depends in biphasic (increasing, then decreasing) manner on the ratio of cell/substratum adhesive force to intracellular motile force — has been demonstrated consistent with experimental comparisons of smooth muscle cell migration on fibronectin and collagen, and of endothelial cell migration on fibronectin in the absence and presence of the soluble receptor-binding competitor echistatin. Further, two crucial underlying assumptions of the model have received experimental support: that there is a front vs. rear asymmetry in the physical strength of ligand-receptor-cytoskeleton linkage which can be modulated by chemical changes; and, that the physical force needed to disrupt ligand-receptor or receptor-cytoskeleton linkages varies with the chemical affinity of those linkages. Thus, this model relates biochemical and biophysical properties of molecular components involved in cell migration to a measurable feature of this behavioral function. A central concept emerging from this work is that biochemical and biophysical aspects of molecular interactions are closely related, and that alterations in one can influence the other in useful ways for modulating this, and likely other, cell functions.