Shape-Independent Fluidization in Epithelial Cell Monolayers

TL;DR

This study uncovers a shape-independent mechanism of fluidization in epithelial monolayers, emphasizing the roles of adhesion energy and viscous friction over cell shape in tissue fluidity.

Contribution

It challenges the existing shape-based paradigm by demonstrating fluidization driven by adhesion and friction, and extends the vertex model to include kinetic adhesion effects.

Findings

Reducing cell-cell adhesion increases fluidity without changing cell shape.

Current models are incomplete as they neglect adhesion's kinetic role.

A generalized model incorporating adhesion energy and friction matches experimental data.

Abstract

Tissue fluidity regulates many critical biological processes, including embryonic development, wound healing, and cancer metastasis. In confluent epithelia, where cell packing fraction is effectively fixed, the prevailing paradigm postulates that transitions between solid-like jammed and fluid-like unjammed states are governed by a geometric cell shape index determined by the balance of cortical tension and intercellular adhesion. Here, we challenge this geometric framework by reporting a mode of fluidization in epithelial monolayers that is entirely shape-independent. We observe that reducing cell-cell adhesion triggers a substantial increase in fluidity, yet this occurs without any corresponding change in cell shape, cell density, substrate traction, or junctional line tension. This decoupling of shape and fluidity reveals that current vertex models, which treat adhesion solely as a contribution to interfacial tension, are incomplete. To reconcile these findings, we extend the theoretical framework to account for the dual nature of adhesion -- its thermodynamic role in setting interfacial adhesion energy at the cell-cell junctions and its kinetic role in generating viscous drag as cells slide past their neighbors. This generalized model quantitatively captures the experimental data, demonstrating that the interplay between adhesive energetics and dissipative friction is essential for a complete understanding of epithelial fluidity.