Mechanical Tension Actively Triggers RhoA-Mediated Cell Extrusion

Abstract

Cell extrusion is a fundamental process in tissue homeostasis, morphogenesis, and cancer progression, facilitating the removal of cells either alive or through apoptosis. While biochemical signaling pathways are known to regulate extrusion, recent advances have underscored the importance of mechanical forces in this process. Here, using optogenetic control of RhoA activation in epithelial monolayers combined with Bayesian Inversion Stress Microscopy (BISM) and three-dimensional cell-based modeling, we uncover a counterintuitive mechanism whereby elevated tension, instead of stabilizing the monolayer, actively drives extrusion in highly contractile cells. We show that local RhoA activation enhances myosin II–dependent contractility and F-actin reorganization, which promotes cell stiffening, resulting in localized tension buildup. The ensuing tensile stress amplifies vertical mechanical fluctuations, which in turn trigger cell extrusion. Remarkably, these tension-induced extrusions occur both apically and basally. Furthermore, our findings show that RhoA-mediated contractility is not merely an effector of extrusion but also an active promoter of basal extrusion, independently of caspase activation. Our study demonstrates that tensile stress can directly initiate extrusion events and bias their outcome toward apical or basal fates. By identifying tension as a driver rather than a suppressor of extrusion, this work revises current models of epithelial homeostasis and highlights mechanical control as a targetable axis in disease and regeneration.

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Cite

BibTeX RIS

BibTeX

@misc{wodrascka2026mechanical,
  title = {{Mechanical Tension Actively Triggers RhoA-Mediated Cell Extrusion}},
  author = {Fanny Wodrascka and Tianxiang Ma and Pablo Gottheil and Robin Durand and Lucas Anger and Andreas Schoenit and Mallica Pandya and Manon Arnaud and Tien Dang and Siavash Monfared and Guillaume Charras and René-Marc Mège and Amin Doostmohammadi and Benoit Ladoux and Simon de Beco},
  howpublished = {HAL},
  year = {2026},
  month = jul,
  doi = {10.64898/2026.07.08.737158},
  url = {https://hal.science/hal-05797483v1},
  note = {CC BY-NC-SA 4.0},
}

RIS

TY  - UNPB
TI  - Mechanical Tension Actively Triggers RhoA-Mediated Cell Extrusion
AU  - Fanny Wodrascka
AU  - Tianxiang Ma
AU  - Pablo Gottheil
AU  - Robin Durand
AU  - Lucas Anger
AU  - Andreas Schoenit
AU  - Mallica Pandya
AU  - Manon Arnaud
AU  - Tien Dang
AU  - Siavash Monfared
AU  - Guillaume Charras
AU  - René-Marc Mège
AU  - Amin Doostmohammadi
AU  - Benoit Ladoux
AU  - Simon de Beco
PY  - 2026
DA  - 2026/07/08
PB  - HAL
DO  - 10.64898/2026.07.08.737158
UR  - https://hal.science/hal-05797483v1
AB  - Cell extrusion is a fundamental process in tissue homeostasis, morphogenesis, and cancer progression, facilitating the removal of cells either alive or through apoptosis. While biochemical signaling pathways are known to regulate extrusion, recent advances have underscored the importance of mechanical forces in this process. Here, using optogenetic control of RhoA activation in epithelial monolayers combined with Bayesian Inversion Stress Microscopy (BISM) and three-dimensional cell-based modeling, we uncover a counterintuitive mechanism whereby elevated tension, instead of stabilizing the monolayer, actively drives extrusion in highly contractile cells. We show that local RhoA activation enhances myosin II–dependent contractility and F-actin reorganization, which promotes cell stiffening, resulting in localized tension buildup. The ensuing tensile stress amplifies vertical mechanical fluctuations, which in turn trigger cell extrusion. Remarkably, these tension-induced extrusions occur both apically and basally. Furthermore, our findings show that RhoA-mediated contractility is not merely an effector of extrusion but also an active promoter of basal extrusion, independently of caspase activation. Our study demonstrates that tensile stress can directly initiate extrusion events and bias their outcome toward apical or basal fates. By identifying tension as a driver rather than a suppressor of extrusion, this work revises current models of epithelial homeostasis and highlights mechanical control as a targetable axis in disease and regeneration.
ER  -

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