How cells change shape to heal wounds

The body’s cells adapt their shape to seal wounds and other openings. This repair process depends on the curvature of the gap and the arrangement of the cell’s internal structures.

Epithelial cells form protective linings across body surfaces. They shield against physical injury, microbes, and dehydration while also helping absorb nutrients, expel waste, and produce hormones and enzymes.

Recent research highlights how the endoplasmic reticulum (ER) inside these cells reorganizes. When gaps curve outward, the ER takes tubular shapes. When gaps curve inward, the ER flattens into sheet-like structures.

Cell movement shapes wound healing

The study shows that different forces direct these changes. The forces are linked to the type of movement cells use.

Convex gaps trigger crawling movements where cells spread broad extensions. Concave gaps instead rely on purse-string contractions, where cells tighten and draw edges together.

This dynamic reshaping of the endoplasmic reticulum ensures epithelial cells adapt effectively to their environment.

Mechanisms underlying wound closure

The researchers used micro-patterned cell layers and advanced imaging to track ER organization. They found that ER geometry is not static but highly responsive to mechanical signals. This responsiveness allows cells to coordinate how they close gaps.

“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,” noted Dr. Simran Rawal from the Tata Institute of Fundamental Research.

How cells repair and fight disease

Mathematical modeling confirmed that mechanical cues alone can explain these ER transitions. The models showed how ER reshaping influences both crawling and purse-string movements, supporting efficient wound closure.

“The ER’s role in cell movement is not just a fascinating scientific discovery but also a potential game-changer for various medical treatments and therapies,” said Dr. Pradeep Keshavanarayana.

“Using mathematical models to understand how cells repair themselves may lead to better treatments for wounds, new methods for regenerating damaged tissues, or an improved grasp of how cancer cells spread – leading to new strategies to prevent or slow down metastasis.”

Link between organelles and healing

Professor Fabian Spill from the University of Birmingham noted that the project is a great example of a fruitful interdisciplinary collaboration.

“We previously studied endothelial monolayers, which are the cells that line blood vessels, and investigated how mechanical and geometrical features regulate gaps in the monolayer that can cause leakiness,” said Spill.

The experiments showed a novel, unexpected link between organelle and cell shape and monolayer behavior, he added.

“The combination of these beautiful experiments by Simran and collaborators with the mathematical model developed by Pradeep led to the identification of a new, organelle-mediated mechanism of sensing mechanics and geometry.”

Cells convert mechanical signals

The study also highlights mechanotransduction, where cells convert mechanical signals into biochemical responses. The ER acts as a central sensor during this process.

“This study started with the discovery made by Simran, who observed the ER’s central role in mechanotransduction – the process by which cells convert mechanical stimuli from their environment into biochemical signals,” said study co-author Professor Tamal Das.

He pointed out that mechanotransduction is fundamental to several physiological functions, including touch, hearing, and balance, and has been studied in the context of collective cell migration.

“Our collaboration shaped the theoretical framework and deepened our understanding of the underlying mechanisms. Together, our experiments and modeling reveal a novel role for the ER in this process,” said Professor Das.

Improving future therapies

According to the researchers, these findings expand our understanding of how organelles guide collective cell movement.

Since epithelial migration is central to wound healing, cancer invasion, and tissue regeneration, this research could influence future therapies.

The ER’s ability to reorganize in response to forces makes it a vital player in maintaining tissue integrity and ensuring proper cellular function.

The combined use of experimental observations and mathematical models demonstrates how cellular architecture is deeply connected to health, disease, wound repair, and overall body stability – highlighting its critical role in both healing and long-term survival.

The study is published in the journal Nature Cell Biology.

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