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Research reveals how wounds heal in “waves”



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Many cells in our bodies are moving and somehow seem to “know” where to go. But how to find out the location of your destination? This question is key to understanding phenomena such as cell renewal in our body, the migration of cancer cells and especially how wounds heal. Eduard Hanezo and his team at the Institute of Science and Technology Austria (IST Austria) in collaboration with Tsuyoshi Hirashima and his student at the University of Kyoto propose a new model of information transfer in which cells use self-organizing long-distance traveling waves to close wound. This study was recently published in the journal Physics of nature.


The researchers developed a mathematical model to describe the interactions in a layer of cells on a substrate, similar to a layer of skin. These cells contain chemical signaling agents ̵

1; proteins that allow them to sense other cells around them, so whether they are pushed or pulled, and to control their own movement. What the scientists found was that the complex interactions of cell movement, environmental perception, and protein activation states in cells combine to create related mechanical and chemical traveling waves in which direction information is encoded.

Feedback cycles

The mechanical wave appears as denser and sparser areas of cells, alternating in space and time. The chemical wave appears as protein activity and is triggered by cell movement and mechanical feedback. Cell chemistry, in turn, stimulates the change in cell shape and movement, closing the feedback circuit with cell mechanics. In this connected system, these mechanical and chemical waves occur spontaneously due to feedback and amplification.

In a normal undeveloped layer of cells, these waves propagate without a preferred direction, but when an artificial wound is introduced on one side, the waves are reoriented to propagate extremely far from the wound. In this way, the researchers suggested that the waves could be a means of communication, allowing the cells very far from the wound – and thus not directly “seeing” it – to feel which way to go.

Chemical waves of protein activation observed in a layer of cells. Credit: Tsuyoshi Hirashima

Reading the waves

The density wave causes the cell’s neighbors to push and pull it in the direction the wave is traveling. Since the forces exerted on the cell are equal and opposite between the ridges and troughs of each wave, the result is that the cell simply moves small distances back and forth without any net movement. In fact, the cell has no way of knowing the direction from which the wave came, and thus has no information about the location of the wound.

Here comes the second wave of protein activity. It hits the cell slightly after the density wave due to the delay needed to activate the proteins. And because protein activity controls the speed at which cells move, the delay between the two waves allows cells to move quickly when pulled in the direction of the wound and slowly when pushed out. In this way, the cells can break the symmetry and begin to move in the preferred direction to the wound.

Non-equilibrium experiments

Researchers at Kyoto University observed this imbalance in wound healing during in vitro experiments with real cells on a substrate. They used a new microscopy technique to allow them to measure protein activity in each cell: the protein was modified to glow when activated, thus revealing waves of protein activation propagating in the cell layer. The researchers were able to quantify the wave patterns, which they then also observed experimentally. More strikingly, they also found that the delay between the two waves was close to the theoretically predicted optimum, allowing cells to extract maximum information from the waves.

This mechanism of self-organization is remarkable, as it allows stable and spontaneous communication in the direction of long distances in the cell layers. This shows a way in which coordinated behavior can occur in our bodies, helping them to heal and grow.


Discovering a mechanism for determining the direction of collective cell migration


More information:
Daniel Boocock et al, Theory of mechanochemical modeling and optimal migration in cell monolayers, Physics of nature (2020). DOI: 10.1038 / s41567-020-01037-7, www.nature.com/articles/s41567-020-01037-7

Provided by the Institute of Science and Technology Austria

Quote: The study reveals how wounds heal on “waves” (2020, September 28), extracted on September 28, 2020 from https://phys.org/news/2020-09-reveals-wounds.html

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