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

Worcester Polytechnic Institute, Worcester MA

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Abstract

20*2%. +2(&402 2+/&+1%- /6(34+*%402 %34 +234 +''-( Wu, Min ! # (( +/3425&4+0/3 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. " (( +/3425&4+0/3 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. +) %''+4+0/%- 31%&( +3 /(('(' 53( 20,(&4 (2)02.%/&( +4( 02.%4 %*( 2*%/+8%4+0/%- %.( Worcester Polytechnic Institute ! 04-1508581 42((4 100 Institute Road 42((4 +47 Worcester 05/47 4%4( MA 206+/&( 05/427 USA $+1 034%- 0'( 01609-2280 20,(&4 (2)02.%/&( +4( 0/*2(33+0/%- +342+&43 MA-002 2*%/+8%4+0/%- %.( University of Massachusetts Amherst ! 153926712 42((4 100 Venture Way 42((4 +47 Hadley 05/47 4%4( MA 206+/&( 05/427 USA $+1 034%- 0'( 01035-9450 20,(&4 (2)02.%/&( +4( 0/*2(33+0/%- +342+&43 MA-002 5HY $SSURYHG 7KURXJK 0 %*( 74,7&2 .7*(947 7.3(.5&1 3;*89.,&947 &89 .789 .))1* Wu, Min ! $ ! !** .3897:(9.438 94 574;.)* 9-* 7*6:.7*) .3+472&9.43 .3 9-* +472&9 8-4<3 '*14< !9&79 <.9- 74,7&2 .7*(947 8 7.3(.5&1 3;*89.,&947 8 .89 &11 49-*7 8*3.47 0*> 5*78433*1 .3 &15-&'*9.(&1 47)*7 1&89 3&2* +.789 &2* * 422438 #8*7 &2* 7,&3.?&9.43 41* 43 74/*(9 Wu,Min MINWU3 Worcester Polytechnic PI Institute Sun, Yubing Ybsun1 UMass Amherst co-I Wen,Qi QIWENWPI Worcester Polytechnic co-I Institute " ! " " #" ! &2* 7,&3.?&9.43 41* 43 74/*(9 $ !' # " " # ! " ! # % % " $ !' "# " "# & # ! "#! # $ ! # " " ! # & "# -9958 ,7&398 3.- ,4; 89*2%(*118 7*,.897> (:77*39 -92 + & 85*(.+.( 1.3* (&3349 '* 7*+*7*3(*) &9 9-.8 9.2* .3(1:)* & 89&9*2*39 9-&9 43* +742 9-* *,.897> <.11 '* :8*) ■ ! 5HY $SSURYHG 7KURXJK 4 &,* ! # $ :2'*7 9-* 5&,*8 (438*(:9.;*1> 9-74:,-4:9 9-* &551.(&9.43 4 349 :8* 8:++.=*8 8:(- &8 & '