Molecular Tension Sensors Research Articles

The integrin is a cell-membrane receptor that mediates cell attachment to the extracelluar matrix (ECM). As mechanosensors, integrins also sense and transduce mechanical information of ECM into the cells to regulate cell morphology and migration. Cellular traction forces applied through an ensemble of integrins have been extensively characterized but the cellular tension on a single integrin that needs to be sustainably applied is unknown. Here we developed a molecular tension sensor to measure the tension at a single integrin during cell adhesion to ECM. The ligand of integrin αVβ3, cyclic RGDfK peptide, is synthesized and immobilized to a polymer-passivated surface through a variety of tethers with various rupture forces ranging from 15 pN to 50 pN. During cell adhesion, integrins bind to RGDfKs and transduce tension to the tether. When the tension exceeds its defined tolerance, the tether is ruptured and the ligand separates away from the surface so that the cell does not adhere. A tension titration test with nine different tethers of differing tension tolerance was performed on CHO-K1 cells. We found that cells only adhere and spread on the surface with a tension tolerance of 30 pN or higher. Other cell lines were also tested including HEK 293, MDA-MB-231, Hela cells and NIH/3T3 cells. Despite the large variations in the bulk traction forces known to exist among these cells, the critical tension tolerance required remained at 30 pN. We therefore propose that cells apply a universal tension across a single integrin-ligand pair during cell adhesion. The underlying molecular mechanisms for the universal molecular tension is under investigation. Our approach is generally applicable to other cellular signaling processes and may reveal the physiologically relevant tension magnitudes across single receptor-ligand pairs using a cell physiology readout.