A dynamic 3D Vertex model of stratified epithelia predicts biomechanical drivers of cell delamination*

Cell delamination occurs when a cell in the basal layer of a stratified epithelium detaches from the basement membrane and moves upward into the suprabasal layer. This process helps drive epithelial tissue morphogenesis and maintains tissue homeostasis. However, the mechanisms that drive delamination remain unclear. Although some delamination events are coupled to cell division, we focus here on the simpler case where delamination occurs in the absence of cell division. We perform simulations of a 3D Vertex model extended to represent stratified epithelia. Experimental data from the developing mammalian epithelium have identified specific changes to the transcriptome of cells committed to delamination, suggesting several hypotheses for the mechanisms that drive delamination, including: i) changes in the adhesion of basal cells to extracellular matrix in the basement membrane, ii) local fluidization of surrounding tissue due to cell shape changes and fluctuations, and iii) changes to heterotypic interfacial tensions at the basal-suprabasal interface. We incorporate these effects as specific changes to the model parameters, and make quantitative predictions for cell shapes, delamination probabilities, that we compare directly to experiments, in both control and perturbed systems.