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Published April 18, 2023 | Published
Journal Article Open

Mechanical basis and topological routes to cell elimination


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.

Additional Information

© 2023, Monfared et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. SM is grateful for the generous support of the Rosenfeld Foundation fellowship at the Niels Bohr Institute, University of Copenhagen. SM, GR, and JA acknowledge support for this research provided by US ARO funding through the Multidisciplinary University Research Initiative (MURI) grant no. W911NF-19-1-0245. AD acknowledges funding from the Novo Nordisk Foundation (grant no. NNF18SA0035142 and NERD grant No. NNF21OC0068687), Villum Fonden grant no. 29476, and the European Union via the ERC-Starting Grant PhysCoMeT. The authors would like to thank Dr. Lakshmi Balasubramaniam and Prof. Benoît Ladoux (Institut Jacques Monod, University Paris City), Guanming Zhang and Prof. Julia M Yeomans (The Rudolf Peierls Centre for Theoretical Physics, University of Oxford), Prof. Jörn Dunkel (Mathematics Department, MIT), and Prof. M Cristina Marchetti (Department of Physics, University of California Santa Barbara) for helpful discussions. The authors are also grateful for the comments and the feedback provided by the anonymous reviewers. Data availability. The current manuscript is a computational study, so no data have been generated for this manuscript. Modelling code is uploaded on the first author's GitHub page (https://github.com/siavashmonfared/siavashmonfared.github.io copy archived at Monfared, 2023).

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August 22, 2023
October 23, 2023