Condensation tendency and planar isotropic actin gradient induce radial alignment in confined monolayers.

Tianfa Xie,Lauren E Brown,Sarah R St Pierre,Nonthakorn Olaranont,Yubing Sun,Min Wu

doi:10.7554/elife.60381

Tianfa Xie, Lauren E Brown + Show 4 more

Open Access

https://doi.org/10.7554/elife.60381

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Abstract

A monolayer of highly motile cells can establish long-range orientational order, which can be explained by hydrodynamic theory of active gels and fluids. However, it is less clear how cell shape changes and rearrangement are governed when the monolayer is in mechanical equilibrium states when cell motility diminishes. In this work, we report that rat embryonic fibroblasts (REF), when confined in circular mesoscale patterns on rigid substrates, can transition from the spindle shapes to more compact morphologies. Cells align radially only at the pattern boundary when they are in the mechanical equilibrium. This radial alignment disappears when cell contractility or cell-cell adhesion is reduced. Unlike monolayers of spindle-like cells such as NIH-3T3 fibroblasts with minimal intercellular interactions or epithelial cells like Madin-Darby canine kidney (MDCK) with strong cortical actin network, confined REF monolayers present an actin gradient with isotropic meshwork, suggesting the existence of a stiffness gradient. In addition, the REF cells tend to condense on soft substrates, a collective cell behavior we refer to as the 'condensation tendency'. This condensation tendency, together with geometrical confinement, induces tensile prestretch (i.e. an isotropic stretch that causes tissue to contract when released) to the confined monolayer. By developing a Voronoi-cell model, we demonstrate that the combined global tissue prestretch and cell stiffness differential between the inner and boundary cells can sufficiently define the cell radial alignment at the pattern boundary.

Highlights

The collective migration and rearrangement of cells play a critical role in various biological processes such as morphogenesis (Friedl et al, 2004), wound healing (Gurtner et al, 2008), and cancer metastasis (Trepat et al, 2012)
New to the active dewetting process, we show that when confined in circular mesoscale patterns on rigid substrates, the boundary rat embryonic fibroblasts (REF) cells can robustly develop radial alignment in mechanical equilibrium
Epithelial cells are often modeled as polygon arrays, and the mechanical states are described by the active stress between neighboring cells (Farhadifar et al, 2007; Bi et al, 2016; Tetley et al, 2019)

Summary

Introduction

The collective migration and rearrangement of cells play a critical role in various biological processes such as morphogenesis (Friedl et al, 2004), wound healing (Gurtner et al, 2008), and cancer metastasis (Trepat et al, 2012). Polygonal-cell-based models, such as Vertex models and Voronoi models have been developed to understand how cell-cell adhesion, contractility, and self-propulsion determine cell topography (Farhadifar et al, 2007), single-cell motility (Bi et al, 2016), and collective migration (Tetley et al, 2019). Theories of active nematic liquid crystals have been applied to cell monolayers to understand the cell organization in various cell types such as NIH-3T3 fibroblasts (Duclos et al, 2017), neural progenitor cells (Kawaguchi et al, 2017), and myoblast cells (Blanch-Mercader et al, 2021a; Blanch-Mercader et al, 2021b). A general observation obtained in these cell systems is that cells align their shapes with one another, and eventually form half-integer

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