Multiscale modeling of fluidity in partial EMT (pEMT) planar tissues

PROJECT SUMMARY (See instructions): To date, the studies on tissue fluidity are limited to the epithelial-tissue paradigm, while a variety of tissue migration and morphogenesis involves cells in the partial epithelial-mesenchymal-transition (pEMT) state, including abnormal early development, tissue regeneration, and cancer growth, The long-term objective of the project is to unravel how to control tissue fluidity and flows with cells pocessing the hybrid epithelial/mesenchymal phenotype along the pEMT spectrum. Different from epithelial tissues, pEMT cell monolayers present a unique spatial distribution of force-bearing actin network, and it is not clear how tissue flow and fluidity is facilitated spatiotemporally in the pEMT tissue. The project aims to investigate the fluidity patterning in the partial EMT state at the large-scale tissue level and cell-cell aggregate level. To achieve the goal, we will develop a multiscale theory-experiment framework to elucidate the cell-cell intercalation and large-scale kinematics regulation in the in vitro tissue monolayer induced by a profound wounds. To investigate the distinction of the partial EMT state to the epithelial state in the fluidity control, we will study cell lines with different EMT potential under different treatment conditions that change their extent of partial EMT state and protocols known to perturb cell intercalations and tissue flow. To describe the large-scale tissue flow, we will leverage the morphoelasticity theory and develop novel numerical methods which solve the coupled system of nonlinear elliptic and time-evolution equations by constrained nonlinear optimizations. To describe the cell-cell intercalations among the tissue flow, we will hybrid the morphoelasticity theory with cell-cell junctional kinematics and mechanics, and solve the multiscale system as a nonlinear optimzation problem.