When we think of wound healing, we normally think of wounds to our skin. But wounds happen inside the body in all sorts of tissues and organs, and can have implications in many chronic diseases such as diabetes and asthma. Wounds also favour cancer progression by providing a physical and chemical environment that promotes the invasion of malignant cells.
Now, a group at the Institute for Bioengineering of Catalonia (IBEC) has found a new way to decipher the mechanisms of wound healing, and by doing so has uncovered a new understanding of how cells move and work together to close a gap in a tissue.
Map of the physical forces exerted by cells during wound healing. Cells are labelled in blue, forces are shown in red and yellow, and the wound is the central black region.
This work, published today in Nature Physics, signifies a big step forward in unravelling the mystery of how wounds are repaired and could eventually help with the development of drugs to enhance or quicken healing.
It’s been known for a while that two different mechanisms contribute to wound healing. One is the ‘purse-string’ method, where a ring of contractile proteins forms at the edges of the wound and tightens like the strings of a purse. The other one is ‘cell crawling’, when cells themselves throw out ‘arms’ called lamellipodia to drag themselves along to close the gap. In some wounds, both mechanisms are thought to occur simultaneously, and in others, only one of the two is used.
The IBEC group, together with their collaborators at the IRB, UPC and UB in Barcelona, the University Paris-Diderot, the Mechanobiology Institute of Singapore and the University of Waterloo in Canada, pioneered a technique to measure the nano-scale forces behind wound healing and, in doing so, they discovered that the two currently accepted mechanisms are not sufficient to fully explain the phenomenon. Instead, they showed that a new mechanism applies, in which cells assemble supracellular-contractile arcs that compress the tissue under the wound. By combining experiments and computational modeling, the authors showed that contractions arising from these arcs make the wound heal in a quicker and more robust way.
“It had been long recognized that wound healing could not be fully understood without a direct measurement of the forces that drive cell movement,” explains Xavier Trepat, head of IBEC’s Integrative Cell and Tissue Dynamics group and ICREA research professor. “We’re the first researchers to develop technology to make these measurements, but we’d never expected to stumble over such an extraordinary mechanism of wound repair.”
Being able to optimize tissue repair is a major need for the treatment of acute and chronic diseases. The discovery of the basic mechanism reported in this study is a major step in the quest to achieve effective organ regeneration.
Reference article: Agustí Brugués, Ester Anon, Vito Conte, Jim H. Veldhuis, Mukund Gupta, Julien Colombelli, José J. Muñoz, G. Wayne Brodland, Benoit Ladoux, Xavier Trepat (2014). Forces driving epithelial wound healing. Nature Physics 10, 683–690