Theory of adhesion-driven self-organisation in growing tissues

TL;DR

This paper presents a unified theoretical model linking cell adhesion, self-diffusion, and proliferation to tissue invasion and pattern formation, revealing how adhesion strength influences tissue cohesion and morphology.

Contribution

It develops a multiscale mechanistic framework that explains how adhesion regulates tissue invasion, patterning, and morphogenesis in growing cell populations.

Findings

Weak adhesion leads to stable tissue invasion fronts.

Increased adhesion causes pattern formation and fingering morphologies.

Density-dependent adhesion regulation suppresses instabilities.

Abstract

Cell invasion and spatial pattern formation are two distinct manifestations of cellular self-organisation in development, regeneration, and disease. Here, we develop and analyse a unified theoretical framework that links these two seemingly different behaviours within a single mechanistic model for adhesion-mediated self-organisation in growing cell populations. Using a multiscale analysis, we show that the balance between cell-cell adhesion, self-diffusion, and proliferation controls the emergence of distinct collective dynamics. We find that for weak adhesion, tissues invade through stable monotone fronts. As adhesion increases, invasion slows, fronts become unstable, leading to aggregates and spatial patterns emerging behind the advancing edge. In two spatial dimensions, these instabilities generate fingering morphologies reminiscent of dysregulated invasion in cancer. Crucially, we show that density-dependent regulation of adhesion suppresses these instabilities and restores cohesive tissue expansion. Together, our results identify adhesion strength and its regulation as key determinants of whether tissues invade cohesively or fragment into patterns, and provide a unified framework for understanding collective migration, morphogenesis, and dysregulated growth.