A phenomenological multiscale framework for orientational interactions and viscoelasticity in migrating epithelial monolayers

Abstract

Collective migration of epithelial monolayers emerges from the interplay between mechanical interactions and biochemical signalling. Here, we present a phenomenological mechanobiological framework linking cell-scale orientational interactions to tissue-scale mechanics. We distinguish reversible and irreversible head-on and glancing collisions, showing that reversible interactions store orientational mechanical energy while preserving collision geometry, whereas irreversible interactions dissipate energy and alter cell orientation. The balance between energy storage and dissipation governs collective migration, mechanical feedback, and density-dependent processes including cell jamming and live cell extrusion. These interactions regulate cell elasticity, contractility, and adhesion, thereby modifying epithelial surface tension and the effective viscoelastic response of the monolayer. We quantify these effects using orientational interaction potentials, an effective second virial coefficient, and dimensionless measures of stored and dissipated orientational energy. The relative contribution of these mechanisms increases with cell packing density, becoming dominant near the jamming transition. This framework provides a constitutive interpretation connecting collision-induced orientation dynamics with emergent epithelial rheology and suggests how density-dependent interaction regimes shape collective migration and tissue viscoelasticity.