Traction Forces Control Cell-Edge Dynamics and Mediate Distance Sensitivity during Cell Polarization

Traction forces are generated by cellular actin-myosin system and transmitted to the environment through adhesions. They are believed to drive cell motion, shape changes, and extracellular matrix remodeling [1 -3] . However, most of the traction force analysis has been performed on stationary cells, investigating forces at the level of individual focal adhesions or linking them to static cell parameters, such as area and edge curvature [4-10] . It is not well understood how traction forces are related to shape changes and motion, e.g., forces were reported to either increase or drop prior to cell retraction [11-15]. Here, we analyze the dynamics of traction forces during the protrusionretraction cycle of polarizing fish epidermal keratocytes and find that forces fluctuate together with the cycle, increasing during protrusion and reaching maximum at the beginning of retraction. We relate force dynamics to the recently discovered phenomenological rule [16] that governs cell-edge behavior during keratocyte polarization: both traction forces and probability of switch from protrusion to retraction increase with the distance from the cell center. Diminishing forces with cell contractility inhibitor leads to decreased edge fluctuations and abnormal polarization, although externally applied force can induce protrusion-retraction switch. These results suggest that forces mediate distance sensitivity of the edge dynamics and organize cell-edge behavior, leading to spontaneous polarization. Actin flow rate did not exhibit the same distance dependence as traction stress, arguing against its role in organizing edge dynamics. Finally, using a simple model of actin-myosin network, we show that force-distance relationship might be an emergent feature of such networks.