Integrin-Dependent Difference in Cell Adhesion and Force Exertion

Abstract

Cell adhesion is mediated by various mechanosensitive integrin receptors. We show that α4β1 and α5β1 respectively mediate cell adhesion in a different manner. Unlike α5β1-RGD ligand binding, α4β1-LDVP ligand binding does not activate cell polarization and migration, lacking the focal adhesion which is a large elongated sub-cellular structure. In addition, integrin α5β1-mediated cell adhesion requires relatively high tension (>33 pN) on RGD ligand binding to activate cell adhesion/spreading, but α4β1-mediated adhesion requires much lower force (<12 pN) on LDVP ligand binding. The level of tension required can be altered by utilizing allosteric Fabs against β1 subunit to alter integrin conformational equilibria. When the extended-open conformation populates at higher population, the tension force required to support cell adhesion decreases. Furthermore, we monitored integrin clustering, integrin β1 activation, and molecular force transmission on ligands with high spaciotemporal resolution to show the dynamic molecular details of cell adhesion. In summary, we found that α4β1 mediates a simple manner of cell adhesion distinguished from typical α5β1 mediated adhesions.