Continuum modeling of fluidic and elastic flow during growth-driven wound closure in partial-EMT cell monolayers

Abstract

Large-scale circular gap closure occurs over a time scale on which cell growth and proliferation become important. Growth is the main driver of the closing process, while cell dynamics such as elongation and intercalation reflect elastic and fluidic contributions to tissue deformation. We develop a novel fluidized growth-elasticity framework as a nonlinear analogue of a Maxwell fluid with growth. The framework decomposes the experimentally observable strain rate into the additive sum of the growth, elastic, and fluidic strain rates, thus enabling the separate quantification of these contributions from tissue kinematics and allowing the roles of tissue elasticity and fluidity (the inverse of viscosity) to be characterized. We apply the model to large circular gaps ($\sim$1.7 mm in diameter) in confluent monolayers of mouse embryonic epicardial cells (MEC1) under two conditions, without and with TGF-$β$ treatment. We show that both tissue fluidity and the elastic properties associated with fiber reinforcement are critical for reproducing the closure kinematics. Specifically, we predict that the treated condition has lower fluidity, associated with a lower fluidic deformation rate and a higher elastic deformation rate than the untreated condition, in agreement with the experimental observations.