Active wetting of epithelial tissues: modeling considerations

Morphogenesis, tissue regeneration, and cancer invasion involve transitions in tissue morphology. These transitions, caused by collective cell migration (CCM), have been interpreted as active wetting/de-wetting transitions. This phenomenon is considered based on a model system as wetting of a cell aggregate on a rigid substrate, which includes cell aggregate movement and isotropic/anisotropic spreading of a cell monolayer around the aggregate depending on the substrate rigidity and aggregate size. This model system accounts for the transition between 3D epithelial aggregate and 2D cell monolayer as a product of: (1) tissue surface tension, (2) surface tension of substrate matrix, (3) cell-matrix interfacial tension, (4) interfacial tension gradient, (5) viscoelasticity caused by CCM, and (6) viscoelasticity of substrate matrix. These physical parameters depend on the cell contractility and state of cell-cell and cell-matrix adhesion contacts, as well as the stretching/compression of cellular systems caused by CCM. Despite extensive research devoted to study cell wetting, we still do not understand the interplay among these physical parameters which induces an oscillatory trend of cell rearrangement. This review focuses on these physical parameters in governing the cell rearrangement in the context of epithelial aggregate wetting/de-wetting, and on modeling approaches aimed at reproducing and understanding these biological systems. In this context, we not only review previously published biophysical models for cell rearrangement caused by CCM, but also propose new extensions of those models to point out the interrelation between cell-matrix interfacial tension and epithelial viscoelasticity and the role of the interfacial tension gradient in cell spreading.