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

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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.

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Abnormal development and cancer growth involve both solid and fluid properties in living tissues, but

understanding their precise impact on pathological processes requires further investigation. This project

aims to develop mathematical theories, numerical methods, and experiments to study how fluidity is

patterned at both tissue and cellular levels during in vitro tissue wound closure.

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