Mechanotransduction in Collective Cell Migration

The collective movement of epithelial cells drives essential multicellular organization during various fundamental physiological processes like embryonic morphogenesis, cancer, and wound healing. Two hallmarks of collective behavior in migrating cohesive epithelial cell sheets is the emergence of so called leader cells and the communication between adjacent cells to move correlated to each other. Here we discuss these two phenomena: (i) The geometry-based cue imposed by the matrix environment like local curvature of the collective’s perimeter is capable of triggering leader cell formation and promoting enhanced motility at defined positions. Cytoskeletal tension was found to be important for geometry induced leader cell formation. Together our findings suggest that high curvature leads to locally increased stress accumulation, mediated via cell-substrate interaction as well as via cytoskeleton tension. The stress accumulation in turn enhances the probability of leader cell formation as well as cell motility. (ii) Within this cohesive group each individual cell correlates its movement with that of its neighbours. We investigate the distinct molecular mechanism that links intercellular forces to collective cell movements in migrating epithelia. More specifically, we identified the molecular mechanism whereby Merlin, a tumor suppressor protein and Hippo pathway regulator that functions as a mechanochemical transducer, coordinates collective migration of tens of hundreds of cells. In the context of collective cell migration, the transmission and mediation of cellular tension is of major importance.

References
1. T. Das, K. Safferling, S. Rausch, N. Grabe, H. Böhm, and J.P. Spatz: A molecular mechanotransduction pathway regulates collective migration of epithelial cells. Nature Cell Biology 2015, 17, 276-287.
2. S. Rausch, T. Das, J.R.D. Soiné, T.W. Hofmann, C.H.J. Böhm, U.S. Schwarz, H. Böhm, and J.P. Spatz: Polarizing cytoskeletal tension to induce leader cell formation during collective cell migration. Biointerphases 2013, 8, 32.