A hybrid multicellular model of tissue formation during epithelial-mesenchymal transition

Epithelial-mesenchymal transition (EMT) is the transdifferentiation of epithelial cells to a mesenchymal phenotype, in which cells lose epithelial-like cell–cell adhesions and gain mesenchymal-like enhanced contractility and mobility. EMT is crucial for tissue regeneration and is also implicated in pathological conditions, such as cancer metastasis. Prior work has shown that transforming growth factor-β1 (TGF-β1) is a potent inducer of this biological process. In this presentation, I will show our recent work to develop a computational model coupling mechanical and biochemical signaling in a multicellular tissue undergoing EMT. We utilize a recently developed formulation that integrates a multicellular cellular Potts model (CPM) with mechanical and biochemical components, specifically, an intracellular signaling TGF-β1-mediated EMT model that governs cellular phenotype; and an extracellular signaling component governing the extracellular matrix (ECM) and TGF-β1 signaling. Simulations predict the spatial patterning that occur in tissue and the ECM during EMT, and variation in model parameters demonstrated conditions enhancing and suppressing EMT. Simulated scratch test experiments illustrate that ECM composition can impact closure directly through EMT signaling. Ongoing and future work will focus on a similar framework to model cancer metastasis dynamics.