Mechanical basis and topological routes to cell elimination

Abstract

Cell layers eliminate unwanted cells through the extrusion process, which underlines healthy versus flawed tissue behaviors. Although several biochemical pathways have been identified, the underlying mechanical basis including the forces involved in cellular extrusion remain largely unexplored. Utilizing a phase-field model of a three-dimensional cell layer, we study the interplay of cell extrusion with cell-cell and cell-substrate interactions, in a flat monolayer. Independent tuning of cell-cell versus cell-substrate adhesion forces reveals that extrusion events can be distinctly linked to defects in nematic and hexatic orders associated with cellular arrangements. Specifically, we show that by increasing relative cell-cell adhesion forces the cell monolayer can switch between the collective tendency towards five-fold, hexatic, disclinations relative to half-integer, nematic, defects for extruding a cell. We unify our findings by accessing three-dimensional mechanical stress fields to show that an extrusion event acts as a mechanism to relieve localized stress concentration.

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Cited by in corpus (7)

• Self-Aligning Polar Active Matter
• Intercellular Friction and Motility Drive Orientational Order in Cell Monolayers
• Multiphase Field Model of Cells on a Substrate: From 3D to 2D
• Cell sorting by active forces in a phase-field model of cell monolayers
• The Cellular Potts Model on Disordered Lattices
• Elasticity tunes mechanical stress localization around active topological defects
• Collective epithelial migration mediated by the unbinding of hexatic defects