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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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Wu,Min MINWU3 Worcester Polytechnic PI
Institute
Sun, Yubing Ybsun1 UMass Amherst co-I
Wen,Qi QIWENWPI Worcester Polytechnic co-I
Institute
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