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Mechanics of Live Cell Elimination

Monfared, Siavash and Ravichandran, Guruswami and Andrade, José E. and Doostmohammadi, Amin (2021) Mechanics of Live Cell Elimination. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20210824-175501480

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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 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.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2021.08.17.456649DOIDiscussion Paper
ORCID:
AuthorORCID
Monfared, Siavash0000-0002-7629-7977
Ravichandran, Guruswami0000-0002-2912-0001
Andrade, José E.0000-0003-3741-0364
Doostmohammadi, Amin0000-0002-1116-4268
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.
Group:GALCIT
Funders:
Funding AgencyGrant Number
Army Research Office (ARO)W911NF-19-1-0245
Novo Nordisk FoundationNNF18SA0035142
Villum Foundation29476
Marie Curie Fellowship847523
Record Number:CaltechAUTHORS:20210824-175501480
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210824-175501480
Official Citation:Mechanics of Live Cell Elimination. Siavash Monfared, Guruswami Ravichandran, José E. Andrade, Amin Doostmohammadi. bioRxiv 2021.08.17.456649; doi: https://doi.org/10.1101/2021.08.17.456649
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:110402
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:24 Aug 2021 18:05
Last Modified:24 Aug 2021 18:05

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