Mechanical Basis for Epithelialization

Epithelial tissues are comprised of sheets of cells that shape animal bodies. The architecture and mechanical integrity of epithelial tissues underlies their function. Our work addresses the question of how physical interactions, such as cell density, stiffness, and cell-cell or cell-substrate connections, affect the development of epithelial tissue architecture. The role played by physical interactions in architecture development is difficult to study in vivo since tissue development is predicated on the existence of physical cell connections. We developed a 2D computational model of epithelia in the plane perpendicular to most existing models of epithelia (such as vertex models), to investigate physical interactions in development. Our model simulates lateral cell surfaces as well as apical and basal tissue surfaces to investigate how physical interactions shape cell morphology. By using cell-cell border length as a readout, we find that a spatial constraint holding cells in proximity is required for the development of tissue architecture. We validated our in vitro predictions in experiments using cultured MDCK cells. Our work suggests that cell density is the primary factor in cell-cell border development and that cell-cell adhesion is subordinate. We are currently working to address the question of how physical constraints affect other epithelial processes.