Cell-Cell Adhesion as a Double-Edged Sword in Tissue Fluidity

TL;DR

This study investigates how cell-cell adhesion's energetic and dissipative components influence tissue fluidity and collective cell migration, revealing a complex interplay that governs tissue mechanics and behavior.

Contribution

It introduces an extended vertex model incorporating junctional viscosity to elucidate the dual, rate-dependent roles of adhesion in tissue dynamics and rheology.

Findings

Increasing energetic adhesion promotes migration and lowers neighbor exchange barriers.

Strengthening dissipative adhesion induces tissue jamming and reduces cell motion.

Adhesion modulates tissue viscoelasticity, affecting relaxation timescales.

Abstract

Cell migration plays a fundamental role in numerous physiological processes, including embryonic development, wound healing, and cancer metastasis. While cell-cell adhesion is known to regulate motion by shaping cell morphology and intercellular force balance, its dynamic, rate-dependent contributions to tissue behavior remain poorly understood. In this study, we examine how the dissipative nature of cell-cell adhesion influences tissue dynamics and collective migration using an extended vertex model with explicit junctional viscosity. Our findings reveal a nontrivial interplay between two distinct components of adhesion: an interfacial adhesion energy (energetic, rate-independent) contribution, which sets the effective junctional tension, and a dissipative (rate-dependent) contribution, which controls resistance to relative motion during cell rearrangements. We show that increasing the energetic component promotes migration by modifying cell shape and lowering the barrier to neighbor exchanges, whereas strengthening the dissipative component induces jamming and suppresses cell motion. Linear rheological analysis further demonstrates that, in the unjammed regime, vertex-model tissues exhibit power-law viscoelastic behavior, with adhesion modulating the power-law exponent and thereby controlling the spread of relaxation timescales. Together, these findings clarify the dual role of adhesion in governing tissue mechanics and rheology and provide a mechanistic framework for understanding the balance between fluidity and rigidity in epithelial monolayers.