Competing mechanisms for the buckling of an epithelial monolayer identified using multicellular simulation

A model using the rigid body multi-cellular framework (RBMCF) is implemented to investigate the mechanisms of buckling of an epithelial mono-layer. Specifically, the deformation of a monolayer of epithelial cells which are attached to a basement membrane and the surrounding stromal tissue. The epithelial monolayer, supporting basement membrane and stromal tissue are modelled using two separate vertex dynamics models (one for the epithelial monolayer layer and one for the basement membrane and stromal tissue combined) and interactions between the two are considered using the RBMCF to ensure biologically realistic interactions. Model simulations are used to investigate the effects of cell-stromal attachment and membrane rigidity on buckling behaviour. We demonstrate that there are two competing modes of buckling, stromal deformation and stromal separation. HighlightsO_LIA rigid body multi-cellular framework allows for the simulation of an epithelial monolayer which is connected to a basement membrane and surrounding tissue stroma. C_LIO_LIInteraction with basement membrane and tissue stroma allows epithelial cells to migrate forming a confluent monolayer. C_LIO_LIBuckling of monolayer can occur through separation from or deformation of the basement membrane. C_LI