In a wounded tissue, the nearby cells move together to close the gap. But they do not all move the same way. Some cells spread out and crawl forward using flat extensions called lamellipodia. Others pull the wound closed like a tightening drawstring, using a mechanism called purse-string contraction. Scientists already know that the shape of the wound edge influences which strategy cells use. Cells at convex edges tend to crawl using lamellipodia. Cells at concave edges are more likely to use purse-string contraction. What has not been clear is how cells sense these shapes and decide which mode of movement to use.

A study published in Nature Cell Biology from the Tata Institute of Fundamental Research (TIFR) Hyderabad helps answer this question. The researchers found that the endoplasmic reticulum (ER) helps cells respond to the wound shape. The ER is usually known for the synthesis and processing of proteins and lipids. But this study shows that ER also changes shape depending on the geometry of the wound edge, and this change helps determine how cells move during wound healing.

To study this, the researchers created controlled wounds in layers of epithelial cells using designed patterns, yielding wound edges with clear convex and concave shapes, using Madin-Darby Canine kidney (MDCK) cells. As expected, cells at convex edges mostly formed lamellipodia and crawled forward. Cells at concave edges were more likely to form thick actin bundles linked to purse-string wound closure. The researchers then examined organelles within these cells to determine whether any behaved differently at the two types of wound edges. While most organelles only changed position, the ER also changed its shape. At convex edges, the ER became more tubular, forming a loose network of tubules. At concave edges, it became more sheet-like, forming denser, flattened structures. A similar pattern was also seen in mouse embryonic skin wounds, showing that this is not just an artificial lab effect.

But what causes this change in the ER shape? Their results suggest that it is driven by the different forces acting at different wound edges. At convex edges, cells are more protrusive, pushing outward using actin-driven lamellipodia. At concave edges, cells are more contractile, pulling inward using actomyosin. When the researchers blocked the protrusive activity, cells at both edge types became more contractile, and the ER shifted toward the sheet-like form. When they blocked contractility, cells became more protrusive, and the ER shifted toward the tubular form. They also used a light-controlled method to trigger local protrusions, which made the ER in that region more tubular. These experiments showed that the ER is not static. It responds dynamically to the mechanical activity in the cell.

The study also showed that microtubules are closely involved in this process. At convex edges, where the ER becomes tubular, microtubules tend to be arranged perpendicular to the wound edge. At concave edges, where the ER becomes sheet-like, microtubules are more often aligned parallel to the edge. When the researchers disrupted the microtubules, the tubular ER network could no longer form properly. Thus, microtubules help organise the tubular ER network specifically at convex edges of the wound, whereas the sheet-like ER seen at concave edges forms through a different mechanism that does not rely on microtubules.

A key question was whether the ER is just responding to what the cell’s action (or behaviour) is doing, or whether it actually helps control cell’s movement. To test this, the researchers changed the ER shape by increasing proteins that promote either ER tubules or ER sheets. When they increased ER tubules, cells became more likely to form lamellipodia and crawl forward-even in places where they would normally prefer purse-string contraction. When they increased ER sheets, the opposite happened: cells were less likely to make lamellipodia and more likely to pull inward. It showed that the ER shape is not just a secondary effect. It actively influences how cells migrate during wound closure.

The researchers also found a likely way the ER influences cell movement: through focal adhesions. These are structures that help cells attach to the surface beneath them and transmit forces during movement. Tubular ER was associated with focal adhesions that support forward crawling, while sheet-like ER was associated with those that support purse-string contraction. This suggests that the ER helps organise the cell’s internal mechanics and attachments so that the right type of movement happens at the right wound geometry.

This study understands an unexpected role for the endoplasmic reticulum in wound healing. It shows that the ER can act as a shape-sensitive and force-responsive structure inside the cell. By changing between tubular and sheet-like forms, it helps cells interpret the geometry of a wound edge and choose whether to crawl or contract. This reveals how tissues heal and how we think about the ER better.