Ivana Pajić-Lijaković, M. Milivojevic, Peter V. E. McClintock

2026.3.14Advances in Physics-X

DOI: 10.1080/23746149.2026.2643751

Abstract

Epithelial fingering emerges when the free edge of a collectively migrating monolayer becomes mechanically unstable. Inhomogeneous line tension and spatial differences in adhesion energy relative to cell–cell cohesion guide cells toward mechanically favorable regions at finger tips. This edge-directed migration locally disrupts adherens junctions, promotes leader cell formation, and amplifies protrusive instabilities. Because fingering breaks edge continuity, it perturbs coordinated migration, weakens mechanical coherence, and compromises epithelial integrity during wound closure, morphogenesis, and barrier maintenance. Preventing fingering is therefore essential for preserving directional migration and tissue cohesion. Monolayer viscoelasticity critically regulates this behaviour. Time-dependent redistribution of residual stresses controls energy storage and dissipation and modulates effective edge line tension. Spatial variations in cell packing density generate isotropic or anisotropic migration patterns that shape in-plane stress gradients and trigger local wetting or de-wetting. Formation of a continuous supracellular actin cable increases line tension and stabilizes the edge, thereby suppressing fingering. Together, these mechanisms provide a theoretical framework linking spatial heterogeneity, viscoelastic stress redistribution, and edge mechanics to the emergence and control of epithelial fingering.

Citation format

PAJIĆ-LIJAKOVIĆ, Ivana; MILIVOJEVIC, M.; MCCLINTOCK, Peter V. E. Mechanical instabilities in epithelial monolayers: Viscoelasticity, line tension, and wetting-driven fingering. Advances in Physics-X, 2026.