Mechanical basis and topological routes to cell elimination

TL;DR

This study uses a phase-field model to explore the mechanical forces and topological defects involved in cell extrusion within tissue layers, revealing how adhesion forces influence cellular arrangements and stress relief during extrusion.

Contribution

It introduces a mechanical and topological framework for understanding cell extrusion, linking adhesion forces to defect types and stress distribution in tissue monolayers.

Findings

Extrusion is linked to defects in nematic and hexatic order.

Increasing cell-cell adhesion shifts defect dominance from nematic to hexatic.

Extrusion relieves localized mechanical stress in cell layers.

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.