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Biomechanics of epithelial cell islands analyzed by modeling and experimentation

We generated a new computational approach to analyze the biomechanics of epithelial cell islands that combines both vertex and contact-inhibition-of-locomotion models to include both cell-cell and cell-substrate adhesion. Examination of the distribution of cell protrusions (adhesion to the substrate) in the model predicted high order profiles of cell organization that agree with those previously seen experimentally. Cells acquired an asymmetric distribution of protrusions (and traction forces) that decreased when moving from the edge to the island center. Our in silico analysis also showed that tension on cell-cell junctions (and monolayer stress) is not homogeneous across the island. Instead it is higher at the island center and scales up with island size, which we confirmed experimentally using laser ablation assays and immunofluorescence. Moreover, our approach has the minimal elements necessary to reproduce mechanical crosstalk between both cell-cell and cell substrate adhesion systems. We found that an increase in cell motility increased junctional tension and monolayer stress on cells several cell diameters behind the island edge. Conversely, an increase in junctional contractility increased the length scale within the island where traction forces were generated. We conclude that the computational method presented here has the capacity to reproduce emergent properties (distribution of cellular forces and mechanical crosstalk) of epithelial cell aggregates and make predictions for experimental validation. This would benefit the mechanical analysis of epithelial tissues, especially when local changes in cell-cell and/or cell-substrate adhesion drive collective cell behavior.