Macroscopic patterns of tractions, stress, and proliferation in freely-expanding and externally driven epithelia.

The collective coordination of mechanical forces and cell division at a tissue-wide scale is hallmark of several biological processes, ranging from wound healing to embryogenesis. Although the relationship between mechanical cell-cell stress and proliferation is well understood at a biomolecular O(nm) and cellular scale O(µm), there is a distinct lack of empirical measurements of forces and proliferation patterns at a tissue-wide, physiological scale O(mm-cm). Here, we explore the relationship between active cell-substrate tractions, cell-cell stresses, and cell cycle in freely-expanding epithelia beginning at confluence and continuing through full contact inhibition. We then perform similar measurements in externally driven epithelia leveraging electrotaxis—directed cell migration under ionic currents—to program large-scale patterns of collective migration in the tissue. We compare active force production and proliferation rates at the edge of the epithelium to that in the ‘bulk’, motivated by the subdivision of healing epithelia into distinct zones of migratory vs. proliferative behavior. Finally, we present preliminary data characterizing the role of cytoskeletal and junctional structures in these patterns of force production and proliferation using pharmacological inhibition and quantitative imaging.