Mechanical instabilities in epithelial monolayers : viscoelasticity, line tension, and wetting-driven fingering

The phenomenon of epithelial fingering arises from mechanical instabilities at the free edge of collectively migrating cell monolayers. This process is driven by heterogeneous line tension and variations in adhesion energy relative to cell-cell cohesion, directing cells towards mechanically advantageous regions at finger tips. Such edge-directed migration leads to localized disruption of adherens junctions, fostering the development of leader cells and exacerbating protrusive instabilities. Fingering compromises edge continuity, thereby disrupting coordinated cellular migration, diminishing mechanical coherence, and impairing epithelial integrity during vital biological processes such as wound healing, morphogenesis, and barrier function. Consequently, the prevention of fingering is crucial for maintaining directional migration and tissue cohesion. Monolayer viscoelasticity plays a

critical role in modulating this behavior. The temporal redistribution of residual stresses governs energy storage and dissipation, influencing the effective line tension at the epithelial edge. Furthermore, spatial variations in cell packing density induce isotropic or anisotropic migration patterns, which in turn shape in-plane stress gradients and can initiate local wetting or de-wetting phenomena. The establishment of a continuous supracellular actin cable has been shown to augment line tension and stabilize the epithelial edge, effectively suppressing fingering. Collectively, these identified mechanisms establish a comprehensive theoretical framework that connects spatial heterogeneity, viscoelastic stress redistribution, and edge mechanics to the initiation and regulation of epithelial fingering.

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