The role of mechanical interactions in EMT.

The detachment of cells from the boundary of an epithelial tissue and the subsequent invasion of these cells into surrounding tissues is important for cancer development and wound healing, and is strongly associated with the epithelial-mesenchymal transition (EMT). Chemical signals, such as TGF-ß, produced by surrounding tissue can be uptaken by cells and induce EMT. In this work, we present a novel cell-based discrete mathematical model of mechanical cellular relaxation, cell proliferation, and cell detachment driven by chemically-dependent EMT in an epithelial tissue. A continuum description of the model is then derived in the form of a novel nonlinear free boundary problem. Using the discrete and continuum models we explore how the coupling of chemical transport and mechanical interactions influences EMT, and postulate how this could be used to help control EMT in pathological situations.

A free boundary mechanobiological model of epithelial tissues.

In this study, we couple intracellular signalling and cell-based mechanical properties to develop a novel free boundary mechanobiological model of epithelial tissue dynamics. Mechanobiological coupling is introduced at the cell level in a discrete modelling framework, and new reaction-diffusion equations are derived to describe tissue-level outcomes. The free boundary evolves as a result of the underlying biological mechanisms included in the discrete model. To demonstrate the accuracy of the continuum model, we compare numerical solutions of the discrete and continuum models for two different signalling pathways. First, we study the Rac-Rho pathway where cell- and tissue-level mechanics are directly related to intracellular signalling. Second, we study an activator-inhibitor system which gives rise to spatial and temporal patterning related to Turing patterns. In all cases, the continuum model and free boundary condition accurately reflect the cell-level processes included in the discrete model.