Cellular Reorganization Drives Gap Closure in Wound Healing

A recent study has uncovered how epithelial cells—the body’s surface-lining cells—change their internal structures and movement patterns to close gaps such as wounds. Researchers from the U.K .and India, publishing in Nature Cell Biology, demonstrated that the endoplasmic reticulum (ER), a vital organelle within cells, reshapes itself according to the curvature of the gap being repaired.

Epithelial cells serve as barriers against physical harm, pathogens, and dehydration, and play roles in nutrient absorption, waste removal, and substance production, including enzymes and hormones. The study reveals that these cells employ distinct ER structures and movement strategies based on the gap’s shape. When a gap curves outward (convex), the ER forms tube-like configurations; when it curves inward (concave), the ER adopts flat, sheet-like formations.

The researchers identified that mechanical forces—pushing at convex edges and pulling at concave ones—trigger different mechanisms affecting ER shape. For convex edges, cells extend broad, flat protrusions to crawl forward, whereas for concave edges, they contract in a “purse-string” fashion to pull the edges together. Through specialized imaging and mathematical modelling, scientists traced how these changes facilitate the closure of gaps.

Co-author Simran Rawal highlighted the clinical importance of this work: “Wound healing is an important response to injury. Our study opens new avenues for exploring the mechanisms underlying epithelial gap closure and their broader implications for health and disease by identifying a new role of the ER in this process.” Pradeep Keshavanarayana, who developed the mathematical model, added that understanding how the ER coordinates cell movement could inform better treatments for wounds, tissue regeneration, and new strategies against cancer cell spread.