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

Epithelial tissues migrate collectively across complex geometric landscapes during development, repair, and disease, yet how the sign 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.