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Forces exerted by the cells surrounding the gap (dotted blue line) extend away at first, then direct towards the gap during contraction of the purse-string cable (red). Source: IBEC.

Researchers at IBEC reveal that wounds heal using a cellular ‘tug-of-war’

Researchers at IBEC, in a collaboration with their colleagues at the Mechanobiology Institute in Singapore, reveal in a Nature Communications (doi:10.1038/ncomms7111) some surprising mechanics that drive epithelial gap closure in the absence of underlying layers. These scientists have demonstrated that a kind of ‘tug-of-war' takes place after our skin or other epithelial layer is damaged, particularly in cases where the tissue is chronicly or deeply injured. The mechanism identified in this study provides a solid demonstration of how cells exert directional forces to enhance biological processes. 

Usually, in minor or surface wounds, cells begin crawling forward towards the gap, and contractile cables are formed in the cells surrounding the wound to help pull it closed. This mechanism relies on a layer underneath the crawling cells, the extracellular matrix (ECM), which provides a support for them to adhere to and crawl over.

However, in cases of chronic or severe wounds, the underlying layers could also be damaged, and surrounding cells could also be unable to replace the ECM proteins. The researchers wanted to find out how these types of wounds – known as non-adherent gaps – still close and heal, albeit at a slower rate and with an increased likelihood of infection.

“We found that closure of these types of gaps is driven exclusively by the mechanism known as ‘purse-string contraction’,” explains Xavier Trepat, head of IBEC’s Integrative Cell and Tissue Dynamics group. “Using a combination of cell culture, microfabrication and force measurements, we saw that the cells at the edge of the non-adherent gap are still attached to the ECM. They then spread themselves out as far as possible towards the centre of the gap – but measuring the direction of force revealed that they are actually pushing away from it.”

This new knowledge of the mechanical properties of skin and internal epithelial cells may lead to advances in wound repair, especially in cases where the ECM is compromised. With chronic wounds, sores and ulcers a common complication in several diseases, particularly those associated with ageing, it is imperative that researchers better understand the mechanisms at play in their repair.