Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness

Abstract

Migration of cells in higher organisms is mediated by adhesion receptors, such as integrins, that link the cell to extracellular-matrix ligands, transmitting forces and signals necessary for locomotion^1–4. Whether cells will migrate or not on a given substratum, and also their speed, depends on several variables related to integrin–ligand interactions, including ligand levels^5,6, integrin levels^7–9, and integrin–ligand binding affinities^10–12. These and other¹³ factors affect the way molecular systems integrate to effect and regulate cell migration. Here we show that changes in cell migration speed resulting from three separate variables—substratum ligand level, cell integrin expression level, and integrin–ligand binding affinity—are all quantitatively predictable through the changes they cause in a single unifying parameter: short-term cell–substratum adhesion strength. This finding is consistent with predictions of a mathematical model for cell migration¹⁴. The ligand concentration promoting maximum migration speed decreases reciprocally as integrin expression increases. Increases in integrin–ligand affinity similarly result in maximal migration at reciprocally lower ligand concentrations. The maximum speed attainable, however, remains unchanged as ligand concentration, integrin expression, or integrin-ligand affinity vary, suggesting that integrin coupling with intracellular motors remains unaltered.