Research shows how wounds heal in ‘waves’


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Many cells of our body are moving and somehow begin to ‘know’ where to go. But how do they learn the location of their destination? This question is important to understand the phenomena such as renewal of cells in our body, migration of cancer cells and especially how to heal wounds. Ediard Hannezo and his group together with Tsoshi Joshirashima and his student at the University of Kyoto at the Institute of Science and Technology Austria (IST Austria), have proposed a new model of information transfer in which cells use long-distance travel waves in a self-organized manner. She does with To close a wound. This study was recently published in the journal Nature physics.

Researchers created a mathematical model to describe interactions within a layer of cells on a substrate, similar to a layer of skin. These cells have chemical signalers – proteins – that allow them to feel other cells around them, so whether they are pushed or pulled, and to control their own movement. What the scientists found is that complex differences of cell motion, environmental sensing, and protein activation within cells combine to form coupled mechanical and chemical travel waves in which directional information is encoded.

feedback loops

Mechanical waves appear as dense and sparse areas of cells alternating in space and time. The chemical wave manifests as protein activity and is triggered by cell movement and mechanical response. The chemistry of cells in turn changes the shape of the cell and closes the feedback loop with cell mechanics. In this coupled system these mechanical and chemical waves generate spontaneously due to feedback and amplification.

In a normally unwritten layer of cells, these waves propagate in a preferred direction, but when an artificial wound is introduced on one side, the waves are specifically re-oriented to propagate away from the wound. Researchers hypothesized that waves could be a communication device that allowed cells to move far away from the wound – and thus could not “see” directly – making sense of which path to go.

Chemical waves of protein activation are seen in a layer of cells. Sincerely: Tsuyoshi Hirashima

Reading waves

The density wave pushes the neighbors of a cell and pulls it towards the direction in which the wave is traveling. Since the forces exerted on the cell are equal and opposite between the crest and trough of each wave, it results in short distances back and forth without any net motion. In fact, the cell has no way of knowing the wave from the direction and thus has no information about the location of the wound.

This is where the second wave of protein activity comes from. This delay hits the cell after a density wave that takes the protein to activate. And because protein activity controls the speed at which cells move, a delay between two waves allows cells to move quickly when pulled in the direction of the wound, and when pushed away slowly. In this way, cells can break the symmetry and start moving in the preferred direction towards the wound.

Equivalent experiment

Researchers at Kyoto University observed this out-of-balance behavior of wound healing during in vitro experiments with real cells on a substrate. They used a novel microscopy technique to allow them to measure protein activity within each cell: the protein was modified so that it was activated when it became active and that of the protein activation that propagates throughout the cell layer. The waves are exposed. Researchers were able to quantitatively predict wave patterns, which they then also observed experimentally. More explicitly, they also found that the delay between the two waves was close to the theoretically predicted optimum to allow cells to extract maximum information from the waveform.

This mechanism of self-organization is notable for allowing strong and spontaneous communication of direction over large distances within cell layers. It demonstrates a way in which coordinated behavior can occur in our body that helps them to heal and grow.

Discovery of a mechanism to determine the direction of mass cell migration

more information:
Daniel Bukok et al, Principles of Mechanical Chemical and Optimal Migration in Cell Monolayers, Nature physics (2020). DOI: 10.1038 / s41567-020-01037-7,

Provided by the Institute of Science and Technology Austria

Quotes: Research shows how wounds heal in ‘waves’ (2020, 28 September) Retrieved 29 September 2020 from

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