Cellular Sumo Wrestling: Emergent Dynamics following Heterotypic Monolayer Collisions*

Epithelia are stationary under homeostatic conditions. However, it has been recognized for over a century that in response to creation of a wound, epithelial sheets migrate collectively into the empty space. As the wound heals, the two cell sheets collide. Following this collision, the cell layers can either mix or form a stable boundary, but the cellular and biophysical properties determining the behavior of the collective following this collision are not well understood. I will present our group's ongoing work showing a novel biophysical behavior following the heterotypic collision of two monolayers with distinct biophysical phenotypes. We generated a barrier-lift assay with distinct populations of epithelial cells on each side of the wound, one being initially solid-like and stationary, and the other being initially fluidizied and collectively migratory. Upon release of the barrier, the initially solid-like cells moved into the wound in an organized fashion, with wave-like propagation of movement from the leading edge into the bulk of the monolayer, while the initially fluid-like cells moved into the wound area quickly and chaotically. Following the collision of the two cell sheets, an unexpected behavior is observed, wherein the solid-like cells are initially compressed away from the collision site, but then change direction and begin to compress the fluid-like cells, reminiscent of a spring being compressed and then released. These behaviors are complex, emergent, and unexpected. Current work focuses on using traction force microscopy and monolayer stress microscopy to illuminate the underlying physical forces governing this novel phenomenon. I will discuss this project in the larger context of our ongoing efforts to understand how events at the single cell level become integrated to yield collective behavior.