4.8 Article

Mechanical basis and topological routes to cell elimination

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ELIFE
卷 12, 期 -, 页码 -

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eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.82435

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epithelial cells; cell extrusion; collective cell migration; defects in liquid crystals; mechanobiology; biophysics; Other

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Cell layers eliminate unwanted cells through the extrusion process, and the underlying mechanical basis of cellular extrusion remains largely unexplored. By using a phase-field model, the study reveals that the forces involved in cell extrusion are linked to defects in cellular arrangements, and increasing cell-cell adhesion forces can switch the behavior of the cell monolayer for extrusion. An extrusion event acts as a mechanism to relieve localized stress concentration by accessing three-dimensional mechanical stress fields.
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 remains 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 fivefold, 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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