The Force Dynamics of Interacting Cells

We have developed a method to understand the forces that pairs of cells exert upon each other on a surface. When exerting a force or torque on another object, a cell experiences an equal and opposite recoil force, and must therefore brace itself against its substrate. If the substrate is soft and elastic, then absorbing the recoil causes observable displacements of marker particles imbedded below its surface. We here describe a method of traction force microscopy, which can detect and analyze the recoil displacements. We validate our method using a clone of Breast Ductal Epithelial cells, (BDE's), that crawl and interact on collagen coated polyacrylamide substrates of different stiffness. For these cells, noise in the bead data causes random, or “phantom”, forces that fluctuate with standard deviation of approximately 10 nN. In cases where cells are touching, we universally observe significant tension forces that are usually aligned with the centroid-centroid axis of the cell pair. In contrast there are only a few isolated cases where shear forces or torques between BDE cells are above threshold. We also observe that the BDE's exert tension forces in two very different ways; first as part of a “grappling” process which brings the cell membranes into greater contact, and second as the basis for a “tug-of-war,” which has the opposite result. Grappling seems to happen only in the early stages as BDE's pull themselves into alignment. Later on, during the tug-of-war, the cell-cell tension grows and can reach peak values of over 200 nN. In addition, the cell-substrate adhesions near the contact zone are lost.