ULTRA-SENSITIVITY OF CELL ADHESION IN A MECHANICALLY HETEROGENOUS ENVIRONMENT

Cell adhesion regulates critical cellular functions in adherent cells. Yet, the fundamental mechanism during the early events in cell adhesion remains unclear. At the most elementary level, cell processes its environment using single molecular clues for its decision making. Herein, we utilized our recently developed DNA tether called tension gauge tether (TGT) to study the mechanical requirements of integrin-mediated cell adhesion. Our lab showed that cells need to experience a threshold force of 40 pN through single integrin-ligand bonds to initiate adhesion and spreading. We also demonstrated that just a few copies of strong (~ 54 pN) TGTs per cell are enough for cell adhesion and spreading as long as there is a high density of weak tethers. Additionally, we showed that 12 pN and 23 pN tethers, which are unable to induce cell adhesion individually, can induce cell adhesion if they are presented together to the cell. Therefore, the cells appear to be able to perform relative force measurements instead of absolute force measurements. Furthermore, we show by direct single molecule imaging that a cell needs only two copies of 23 pN tethers for such relative force measurements. Moreover, we found that such an observation is due to the presence of relatively stronger tethers that act as membrane holders, which keep the cell membrane close to the surface. Therefore, relatively stronger tethers allow the weaker tethers that are ruptured to re-anneal and subsequently cells remain adhered to the surface