Quantitative predictions of biomechanical drivers of cell delamination in stratified epithelia (skin epidermis) using a dynamic 3D vertex model

During embryonic development, the epidermis transitions from a single-layered stem cell sheet to a stratified, multi-layered tissue through coordinated differentiation and upward movement of basal cells, known as delamination. The mechanisms guiding this process and enabling cells to cross the basal-suprabasal boundary, ensuring tissue homeostasis, remain unclear. We extend the dynamic 3D vertex model to investigate experimentally motivated hypotheses: (i) changes in adhesion of basal cells to the extracellular matrix, (ii) local tissue fluidization driven by cell shape changes and cell divisions, and (iii) autonomous changes in cell-cell adhesion and cortical tension. Transcriptomic data from developing mammalian epithelium, identified by the Niessen and Wickström labs, associate delamination with changes in cell-cell and cell-substrate adhesion pathways. We incorporate these changes into our model as parameter variations in interfacial tensions and substrate adhesion. Although some delamination events are coupled to cell division, we initially focus on cases without division. The model provides quantitative predictions for cell shape, delamination probabilities, and rates, validated against experimental data in control and perturbed conditions to identify key delamination mechanisms.