Abstract
Epithelia have distinct cellular architectures, which are established in development, re-established after wounding, and maintained during tissue homeostasis despite cell turnover and mechanical perturbations. In turn, cell shape also controls tissue function as a regulator of cell differentiation, proliferation, and motility. Here we investigate cell shape changes in a model epithelial monolayer. After the onset of confluence, cells continue to proliferate and change shape over time, eventually leading to a final architecture characterized by arrested motion and more regular cell shapes. Such monolayer remodeling is robust, with qualitatively similar changes in cell shape and dynamics observed across disparate perturbations. Here we quantify differences in monolayer remodeling guided by the active vertex model to identify underlying order parameters controlling epithelial architecture. For instance, for monolayers formed atop extracellular matrix with varied stiffness, we find the cell density at which motion arrests varies significantly but the cell shape remains constant. In contrast, pharmacological perturbations can significantly alter the cell shape at which tissue dynamics is arrested. Remarkably, we find across all experimental conditions the final cell shape is well correlated to the cell proliferation rate. Furthermore, inhibition of the cell cycle immediately arrests both cell motility and shape change, demonstrating that active stress from cell cycle-dependent processes contributes significantly to monolayer remodeling. Thus, the architecture and mechanics of epithelial tissue can arise from an interplay between cell mechanics and stresses arising from cell cycle dynamics.
Competing Interest Statement
The authors have declared no competing interest.