A cellular tug-of-war mechanism forces wounds to close

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Figure: Forces exerted by the cells surrounding the gap (dotted blue line) extend away at first, then direct inwards, towards the gap, during contraction of the 'purse-string' cable (red filaments). Credit: Mechanobiology Institute, National University of Singapore
Figure: Forces exerted by the cells surrounding the gap (dotted blue line) extend away at first, then direct inwards, towards the gap, during contraction of the ‘purse-string’ cable (red filaments). Credit: Mechanobiology Institute, National University of Singapore

In a remarkable study that could have implications for wound healing, scientists from the Mechanobiology Institute (MBI) at the National University of Singapore (NUS) have revealed the mechanical force that drives epithelial wound healing, especially when there is no supporting environment such as (extra cellular matrix (ECM)) below the wound. This research was published in Nature Communications in January 2015.

Skin is a versatile organ that acts as a protective barrier against pathogens and harmful organisms and also helps the body retain various fluids and electrolytes. When this barrier is damaged by cuts or wounds, the consequences could be devastating -the longer the wounds are open. It could lead to ulcers, bleeding and bacterial infections, hence it is of paramount importance that the process of wound healing begins soon.

Scientists have been learning much about how cells coordinate this process of wound healing and repair it. The moment the integrity of the skin is compromised, the epithelial cells of the skin initiates cellular mechanisms to close the gap. Cells begin crawling forward and actin-based contractile cables are formed in the cells surrounding the wound, which helps pull the gap close.This process generally happens with the help of a layer below the skin called extracellular matrix, which provides support for them to adhere to and crawl over.

However, in cases of severe or chronic wounds, the underlying layers containing the ECM could also be damaged. So, the question remained as to how do cells close gaps when the underlying layers are also damaged or when the ECM is eroded?

Scientists revealed that closure of such non-adherent gaps occurs by a mechanism called ‘purse-string contraction’ which is mediated by the co-ordinated action of actin bundles across multiple cells at the edge of the gap. Using a variety of techniques such as traction force microscopy, micro-fabrication, force measurements and cell culture, the scientists discovered that a cellular ‘tug-of-war’ at the gap edge drives the mechanical forces responsible for gap closure.

The cells at the edge of the wound are still attached to the ECM. Force measurements showed that the cells are actually pushing away from the gap initially, stabilizing the cells. Once the cells have spread as far as possible into the gap, the contractile ‘purse-string’ cable forms across the cells, encircling the gap. The force exerted by these cells is reversed and the cells begin to pull each other towards the centre of the gap, aiding gap closure.

As the cells move inwards to close the empty space, more contractile cables can reach out over the gap and connect to the other side. These cables can contract rapidly, leading to the formation of a suspended cell sheet over the gap, and complete closure of the wound.

The ‘tug-of-war’ mechanism identified in this study provides a vivid demonstration of how cells exert directional forces to enhance biological processes. This new knowledge of the mechanical properties of skin and internal epithelial cells may lead to advances in wound healing, especially in cases where the ECM is compromised.

Several diseases show symptoms such as ulcers, wounds and sores and hence knowledge about mechanism underlying the repair process will lead to improved treatments in wound healing.

Source:

http://bit.ly/1DGq1dx

The original publication can be accessed here.