Regulation of intercellular viscosity by E-cadherin-dependent phosphorylation of EGFR in collective cell migration

• DOI: 10.1073/pnas.2405560121
• Publication Date: 2024-09-04T17:55:39Z
• Authors: Chaoyu Fu; Florian Dilasser; Shao-Zhen Lin; Marc Karnat; Aditya Arora; Harini Rajendiran; Hui Ting Ong; Nai Mui Hoon Brenda; Sound Wai Phow; Tsuyoshi Hirashima; Michael Sheetz; Jean-François Rup...; Sham Tlili; Virgile Viasnoff
• Keywords: Adherens junction

Collective cell migration is crucial in various physiological processes, including wound healing, morphogenesis, and cancer metastasis. Adherens Junctions (AJs) play a pivotal role regulating cohesion dynamics during tissue remodeling. While the origin of junctional mechanical tension at AJs have been extensively studied, influence actin cortex structure on junction plasticity remains incompletely understood. Moreover, mechanisms underlying stress dissipation junctions are not well elucidated. Here, we found that ligand-independent phosphorylation epithelial growth factor receptor (EGFR) downstream de novo E-cadherin adhesion orchestrates feedback loop, governing intercellular viscosity via Rac pathway dynamics. Our findings highlight how E-cadherin-dependent EGFR activity controls mode collective movements independently tension. This modulation effective coordinates cellular within expanding monolayer, inducing transition from swirling to laminar flow patterns while maintaining constant front speed. Additionally, propose vertex model with adjustable viscosity, capable replicating all observed phenotypes experimentally.