Wnt Signaling Modulates Mechanotransduction in the Epidermis to Drive Hair Follicle Regeneration

The study investigates the role of Wnt signaling in hair follicle regeneration within the wound-induced hair neogenesis (WIHN) model, where optimal tissue rigidity allows for hair follicle regeneration in wounds. The research reveals that Wnt signaling modulates mechanosensitivity at both cellular and tissue levels, crucial for WIHN. Using atomic force microscopy, the study found a reduced substrate rigidity response in epidermal cells of healing wounds. Super-resolution microscopy and nanoneedle probing showed that Wnt-induced chromatin remodeling significantly decreases nuclear rigidity without affecting nucleocytoskeletal coupling. Wnt signaling also reorganizes actin architecture and recruits adherens junctions, forming a mechanical syncytium that enhances force coordination and collective durotaxis. These findings highlight Wnt signaling's mechanoregulatory role in manipulating mechanotransduction to drive hair follicle regeneration.