Force propagation between epithelial cells depends on active coupling and mechano-structural polarization
- Grenoble Alpes University, France
- Heidelberg University, Germany
- University College London, United Kingdom
Abstract
Cell-generated forces play a major role in coordinating the large-scale behavior of cell assemblies, in particular during development, wound healing and cancer. Mechanical signals propagate faster than biochemical signals, but can have similar effects, especially in epithelial tissues with strong cell-cell adhesion. However, a quantitative description of the transmission chain from force generation in a sender cell, force propagation across cell-cell boundaries, and the concomitant response of receiver cells is missing. For a quantitative analysis of this important situation, here we propose a minimal model system of two epithelial cells on an H-pattern ('cell doublet'). After optogenetically activating RhoA, a major regulator of cell contractility, in the sender cell, we measure the mechanical response of the receiver cell by traction force and monolayer stress microscopies. In general, we find that the receiver cells shows an active response so that the cell doublet forms a coherent unit. However, force propagation and response of the receiver cell also strongly depends on the mechano-structural polarization in the cell assembly, which is controlled by cell-matrix adhesion to the adhesive micropattern. We find that the response of the receiver cell is stronger when the mechano-structural polarization axis is oriented perpendicular to the direction of force propagation, reminiscent of the Poisson effect in passive materials. We finally show that the same effects are at work in small tissues. Our work demonstrates that cellular organization and active mechanical response of a tissue is key to maintain signal strength and leads to the emergence of elasticity, which means that signals are not dissipated like in a viscous system, but can propagate over large distances.
Data availability
All data has been deposited on dryad (https://doi.org/10.5061/dryad.sj3tx9683). All code has been deposited on Github (https://github.com/ArturRuppel/ForceTransmissionInDoublets).
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Force propagation between epithelial cell doubletsDryad Digital Repository, doi:10.5061/dryad.sj3tx9683.
Article and author information
Author details
Ulrich Sebastian Schwarz
Funding
Swiss National Science Foundation (P2LAP3 164919)
- Manasi Kelkar
European Research Council (CoG-647186)
- Guillaume Charras
Agence Nationale de la Recherche (ANR-19-CE13-0028)
- Giovanni Cappello
Centre National de la Recherche Scientifique
- Thomas Boudou
Deutsche Forschungsgemeinschaft (SCHW 834/2-1)
- Ulrich Sebastian Schwarz
Agence Nationale de la Recherche (ANR-17-CE30-0032-01)
- Martial Balland
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Karsten Kruse, University of Geneva, Switzerland
Version history
- Preprint posted: June 3, 2022 (view preprint)
- Received: September 20, 2022
- Accepted: August 7, 2023
- Accepted Manuscript published: August 7, 2023 (version 1)
- Version of Record published: September 20, 2023 (version 2)
Copyright
© 2023, Ruppel et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Force propagation between epithelial cells depends on active coupling and mechano-structural polarization
eLife 12:e83588.
https://doi.org/10.7554/eLife.83588
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