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Published August 24, 2021 | Submitted
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Mechanics of Live 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 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 monolayer. Independent tuning of cell-cell versus cell-substrate adhesion forces in the model reveals that a higher cell-substrate adhesion leads to a lower number of total extrusion events. We find extrusion events to be linked to both half-integer topological defects in the orientation field of the cells and to five-fold disclinations in cellular arrangements. We also show that increasing the relative cell-cell adhesion forces translates into a higher likelihood for an extrusion event to be associated with a five-fold disclination and a weaker correlation with +1/2 topological defects. We unify our findings by accessing mechanical stress fields: an extrusion event acts as a mechanism to relieve localized stress concentration.

Additional Information

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. This version posted August 18, 2021. S.M., G.R. and J.A. acknowledge support for this research provided by US ARO funding through the Multidisciplinary University Research Initiative (MURI) Grant No. W911NF-19-1-0245. A.D. acknowledges support from the Novo Nordisk Foundation (grant no. NNF18SA0035142), Villum Fonden (grant no. 29476), funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 847523 (INTERACTIONS). The authors would like to thank Dr. Lakshmi Balasubramaniam and Prof. Benoît Ladoux (Institut Jacques Monod, Université de Paris), 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.

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Submitted - 2021.08.17.456649v1.full.pdf


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August 20, 2023
October 23, 2023