Aaron Mertz

Cell–cell and cell–matrix adhesions play essential roles in the function of tissues, yet little is known about how crosstalk between these two adhesion types regulate cells’ material properties and active processes. This dissertation combines experiment and theory to reveal how colonies of cells apply forces to the extracellular matrix. Using traction force microscopy, we measure forces transmitted to the substrate by colonies of epithelial cells with strong and weak cadherin-based intercellular adhesions. A minimal physical model in which cell–cell adhesions modulate the physical cohesion between contractile cells is sufficient to recreate the spatial rearrangement of traction forces observed experimentally with varying strength of cadherin-based adhesions. In the limit of very cohesive colonies with strong cell–cell adhesions, our experimental results reveal the emergence of an effective surface tension for cell colonies above a critical size. A minimal model incorporating strong adhesion between cells predicts the observed scaling relationship between total traction force and colony size and that apparent surface tension is determined by the contractility of the actomyosin network. This dissertation delineates the importance of cadherin-based cell–cell adhesions in coordinating mechanical activity and material properties of epithelial tissues. Our findings have implications for the mechanical regulation of epithelial cells during development, homeostasis, and disease.