Systematic AI-assisted screening of the cadhesome to map epithelial monolayer mechanics

Bertocchi C, Alegría JJ, Vásquez-Sepúlveda S, Ibanez-Prat R, Srinivasan A, Arrano-Valenzuela I, Castro-Pereira B, Soto-Montandon C, Trujillo-Espergel A, Montenegro-Rojas I, Deguchi S, Owen GI, Kanchanawong P, Cerda M, Motta G, Zaidel-Bar R, Ravasio A (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Cell Communication and Signaling BioMed Central

Book Volume: 24

Article Number: 505

Journal Issue: 1

DOI: 10.1186/s12964-026-03008-6

Abstract

Cadherin-mediated adhesions serve as key mechanical and signaling hubs in epithelial tissues, linking the actin cytoskeleton of adjacent cells. Their disruption is a hallmark of cancer progression. The “cadhesome” network comprises over 170 proteins involved in cadherin-mediated adhesion and force transmission, yet its complexity hampers functional understanding. We developed a high-throughput platform combining gene silencing, imaging, and AI-based analysis to profile the role of each cadhesome component in monolayer formation and mechanical integrity. Using EpH4 epithelial cells, we analyzed phenotypes under vehicle and nocodazole-challenge conditions. Machine learning enabled classification of monolayer disruption, junctional organization, and contractile state. Beyond confirming known mechanotransduction hubs centered on E-cadherin, EGFR, and RAC1, our approach systematically uncovered candidate regulators of monolayer contractile state and stress adaptation, identified condition-specific roles of poorly characterized proteins, and organized them into annotated mechanobiological subnetworks that serve as a basis for hypothesis generation. Presented as a prioritized discovery resource, this work establishes a scalable strategy to decode mechano-molecular networks and provides a blueprint for hypothesis-driven investigation of epithelial mechanics with potential translational relevance.

Involved external institutions

Pontificia Universidad Católica de Chile CL Chile (CL) Osaka University / 大阪大学 JP Japan (JP) National University of Singapore (NUS) SG Singapore (SG) Universidad de Chile CL Chile (CL) Columbia University US United States (USA) (US) Tel Aviv University IL Israel (IL) Millennium Institute for Data Fundamentals / Instituto Milenio Fundamentos de los Datos CL Chile (CL)

How to cite

APA:

Bertocchi, C., Alegría, J.J., Vásquez-Sepúlveda, S., Ibanez-Prat, R., Srinivasan, A., Arrano-Valenzuela, I.,... Ravasio, A. (2026). Systematic AI-assisted screening of the cadhesome to map epithelial monolayer mechanics. Cell Communication and Signaling, 24(1). https://doi.org/10.1186/s12964-026-03008-6

MLA:

Bertocchi, Cristina, et al. "Systematic AI-assisted screening of the cadhesome to map epithelial monolayer mechanics." Cell Communication and Signaling 24.1 (2026).

BibTeX: Download