Nir Gov's Lab

As wounds heal, embryos develop, cancer spreads, or asthma progresses, the cellular monolayer undergoes a glass transition between solid-like jammed and fluid-like flowing states. During some of these processes, the cells undergo an epithelial-to-mesenchymal transition (EMT): they acquire in-plane polarity and become motile. Thus, how motility drives the glassy dynamics in epithelial systems is critical for the EMT process. However, no analytical framework that is indispensable for deeper insights exists. Here, we develop such a theory inspired by a well-known glass theory. One crucial result of this work is that the confluency affects the effective persistence time-scale of active force, described by its rotational diffusivity, D^eff_r. D^eff_r differs from the bare rotational diffusivity, D_r, of the motile force due to cell shape dynamics, which acts to rectify the force dynamics: D^eff_r is equal to D_r when D_r is small and saturates when D_r is large. We test the theoretical prediction of D^eff_r and how it affects the relaxation dynamics in our simulations of the active Vertex model. This novel effect of D^eff_r is crucial to understanding the new and previously published simulation data of active glassy dynamics in epithelial monolayers.

In this study, we implement the deviatoric curvature model to examine dynamically triangulated surfaces with anisotropic membrane inclusions. The Monte-Carlo numerical scheme is devised to not only minimize the total bending energy of the membrane but also the in-plane nematic order of the inclusions by considering the mismatch between the curvature of the membrane and the intrinsic curvature of the inclusion. Neighboring inclusions can either attract with nearest-neighbor interaction or with a nematic interaction derived from liquid crystal theory. Orientational order determines whether vesicles fully covered with inclusions result in bulbs connected by necks or long tubes. Remarkably, when inclusions on vesicles with no vacancies interact non-nematically, a spontaneous local order can lead to a bulb transition which may have implications in cell or organelle division. Furthermore we find that average nematic order is inversely proportional to the number of thin necks formed in the vesicles. Our method shows good convergence and is suitable for further upgrades, for example to vesicles constrained by volume.

Cells often migrate on curved surfaces inside the body, such as curved tissues, blood vessels, or highly curved protrusions of other cells. Recent in vitro experiments provide clear evidence that motile cells are affected by the curvature of the substrate on which they migrate, preferring certain curvatures to others, termed \u201ccurvotaxis.\u201d The origin and underlying mechanism that gives rise to this curvature sensitivity are not well understood. Here, we employ a \u201cminimal cell\u201d model which is composed of a vesicle that contains curved membrane protein complexes, that exert protrusive forces on the membrane (representing the pressure due to actin polymerization). This minimal-cell model gives rise to spontaneous emergence of a motile phenotype, driven by a lamellipodia-like leading edge. By systematically screening the behavior of this model on different types of curved substrates (sinusoidal, cylinder, and tube), we show that minimal ingredients and energy terms capture the experimental data. The model recovers the observed migration on the sinusoidal substrate, where cells move along the grooves (minima), while avoiding motion along the ridges. In addition, the model predicts the tendency of cells to migrate circumferentially on convex substrates and axially on concave ones. Both of these predictions are verified experimentally, on several cell types. Altogether, our results identify the minimization of membrane-substrate adhesion energy and binding energy between the membrane protein complexes as key players of curvotaxis in cell migration.