Sign of Lateral Curvature Governs Collective Epithelial Migration via Actomyosin Cable Stabilization.

Abstract

Epithelial tissues migrate collectively across complex geometric landscapes during development, repair, and disease, yet how the <i>sign</i> of substrate curvature directs collective migration remains unclear. Here, we introduce a micropatterned gold platform that presents well-defined lateral curvature cues and use it to dissect curvature-guided epithelial migration. We show that epithelial sheets exhibit a pronounced migration hierarchy, advancing preferentially along convex curvatures while delaying migration from concave regions. Convex curvature stabilizes a continuous, tension-bearing actomyosin cable at the migrating front, enabling rapid and coordinated advancement. In contrast, concave curvature destabilizes this architecture, leading to delayed migration and the emergence of lamellipodia-driven protrusive behavior, particularly near geometric inflection points. Concomitantly, cell-cell junctions along convex regions display elevated E-cadherin levels, indicating curvature-dependent reinforcement of intercellular adhesion that supports collective force transmission. Together, these results identify lateral curvature sign as a geometric control parameter that governs collective epithelial migration by coordinating cytoskeletal organization and cell-cell adhesion. This work establishes surface curvature as a cell-instructive material cue and provides design principles for biomaterials that regulate tissue migration and regeneration.