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Friction-induced budding of a cancer cell monolayer

Mathieu Dedenon1,2,3, Jorge Barbazán4,5, Carlos Peréz-González4, Danijela Matic Vignjevic4, and Pierre Sens1,*

  • *Contact author: pierre.sens@curie.fr
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Phys. Rev. Research 8, 023038 – Published 13 April, 2026

DOI: https://doi.org/10.1103/kxwl-2tv1

Abstract

The environment surrounding a tumor plays a crucial role in cancer cell dissemination. Within this microenvironment, cancer-associated fibroblasts (CAFs) can collectively combine their tensile stress to actively remodel tumors. Using in vitro circular clusters of cancer cell monolayers surrounded by CAFs, we generate structures that are reminiscent of multicellular buds observed in vivo for colorectal cancer. A supracellular contractile ring spontaneously assembles at the inner edge of the CAF monolayer and drives its closure on top of the cancer cells through a purse-string mechanism. This CAF-driven constriction triggers multilayering of cancer cells, culminating in the growth of a bud pinched by the CAF ring. We propose that this process is powered by frictional shear stress from CAF motion and develop a theoretical model based on continuum mechanics that quantitatively reproduces the experimental observations. The model captures the early reshaping of the cancer cell layer. Invoking a generic deformation threshold for multilayering, it identifies the physical conditions that favor budding and predicts how budding probability and size scale with initial cluster diameter. Our results establish a general framework for friction-induced morphogenesis in cell layers and reveal how active mechanical coupling between tumors and their microenvironment can shape tumor morphology and behavior.

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Phys. Rev. Research 8, 023038– Published 13 April, 2026
  • Received 27 March 2024
  • Accepted 27 January 2026
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Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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