Fibronectin matrix remodelling modulates the active nematic dynamics of cancer-associated fibroblasts

Jacques C, Perrin L, Ackermann J, Bell S, Zajac O, Lapierre A, Anger L, Hallopeau C, Pérez-González C, Balasubramaniam L, Trepat X, Ladoux B, Maitra A, Voituriez R, Matic Vignjevic D (2026)


Publication Type: Journal article

Publication year: 2026

Journal

DOI: 10.1038/s41563-026-02615-5

Abstract

Cancer-associated fibroblasts are major architects of the tumour stroma, where their aligned, elongated morphology forms a capsule that mechanically restrains tumour expansion. However, it is unclear how this supracellular organization emerges and persists. Here we show that fibroblasts generate a fibronectin matrix that progressively acquires the same nematic order as the cell layer, and that this matrix in turn feeds back to immobilize both cells and topological defects. Using long-term live imaging, traction force microscopy, matrix microfabrication and hydrodynamic modelling, we find that this reciprocal coupling induces an ageing process in which cellular flows and defect motion slow dramatically and ultimately freeze. Despite this arrest, the monolayer remains active, with defects concentrating contractile forces that may represent mechanical weak points. Disrupting fibronectin production fluidizes the capsule, reactivates defect dynamics and compromises its barrier-like function. These findings reveal a self-organizing mechanism by which fibroblasts and their matrix co-evolve to create a mechanically stable, yet active, stromal architecture with direct implications for tumour dissemination.

How to cite

APA:

Jacques, C., Perrin, L., Ackermann, J., Bell, S., Zajac, O., Lapierre, A.,... Matic Vignjevic, D. (2026). Fibronectin matrix remodelling modulates the active nematic dynamics of cancer-associated fibroblasts. Nature Materials. https://doi.org/10.1038/s41563-026-02615-5

MLA:

Jacques, Cécile, et al. "Fibronectin matrix remodelling modulates the active nematic dynamics of cancer-associated fibroblasts." Nature Materials (2026).

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