Substrate-Ligand Friction Controls Traction Force in Cell Adhesion

Abstract

Extracellular matrices determine cell fate decisions through the regulation of intracellular force and stress. The mechanical properties of these matrices like stiffness and ligand anchorage cause a distinct signaling behavior of adherent cells in respect to adhesion receptor forces. This process is known to be tightly linked to downstream kinase activation and epigenetic events including cell proliferation and differentiation. We report now on a new mechanism controlling traction forces in cell adhesion originating from sliding friction between adhesion ligands and the supporting material.Using polymer surfaces with a graded physicochemistry we were able to tune the non-covalent anchorage of adhesion ligands, namely fibronectin, to the materials surfaces. Traction force cytometry and in situ analysis of cell-driven ligand reorganization revealed a correlated dependence on the ligand-substrate anchorage. Ligand reorganization during the formation of fibrillar adhesions was characterized by a reaction-diffusion process with a surface mobility around 1e4 m/Ns. Based on these quantitative data we could describe the force-velocity equilibrium at the adhesion site with its extracellular and intracellular components, namely the nanoscale friction of adhesion ligands on the materials surface and the myosin motor activity at the actin stress fibers. The correlation of a linearized Tomlinson model of ligand friction on the materials surface with the characteristics of myosin motors in the actin stress fibers revealed a control mechanism of traction forces of around 1pN per receptor-ligand pair by the ligand-substrate friction.These findings elucidate a novel mechanism in force regulation at adhesion receptors, which is proposed to be highly relevant for cell behavior on natural and artificial scaffolds in vivo and in vitro, as many adhesion ligands are found non-covalently anchored to scaffold surfaces.