Wound-healing waves

September 28, 2020

Many cells in our bodies are on the move and somehow seem to "know" where to go. But how do they learn the location of their destination? This question is key to understanding phenomena such as the renewal of cells in our body, the migration of cancer cells, and especially how wounds heal. Edouard Hannezo and his group at the Institute of Science and Technology Austria (IST Austria) in collaboration with Tsuyoshi Hirashima and his student at Kyoto University propose a new model of information transfer in which cells utilize long-distance traveling waves in a self-organized manner to close a wound. This study was recently published in the journal Nature Physics.

The researchers built a mathematical model to describe the interactions within a layer of cells on a substrate, similar to a layer of skin. These cells contain chemical signalers--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 is that the intricate interplay of cell movement, sensing of the environment, and states of protein activation within the cells combine to create coupled mechanical and chemical traveling waves in which directional information is encoded.

Feedback loops

The mechanical wave appears as denser and sparser regions of cells alternating in space and time. The chemical wave appears as protein activity and is triggered by cell movement and mechanical feedback. The cells' chemistry in turn drives cell shape changes and movement closing a feedback loop with cell mechanics. In this coupled system these mechanical and chemical waves arise spontaneously due to feedback and amplification.

In a normal unwounded layer of cells, these waves propagate without a preferred direction, but when an artificial wound is introduced on one side, waves re-orient to propagate exclusively away from the wound. The researchers thus hypothesized that the waves could be a communication tool, allowing cells very far from the wound--and thus not directly "seeing" it--to sense which way to go.

Reading the Waves

A density wave makes the neighbors of a cell push and pull on it along the direction in which the wave is traveling. Since the forces exerted on the cell are equal and opposite between the crests and troughs of each wave, the result is that the cell just moves small distances back and forth without any net motion. In effect, the cell has no way of knowing the direction the wave came from and thus has no information about the location of the wound.

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

Out-of-equilibrium Experiments

The researchers at Kyoto University observed this out-of-equilibrium behavior of wound healing during in vitro experiments with real cells on a substrate. They used a novel microscopy technique to allow them to measures protein activity within each cell: the protein was modified so that it lit up when activated thus revealing waves of protein activation propagating throughout the cell layer. The researchers were able to quantitatively predict 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 for allowing cells to extract maximum information from the waves.

This mechanism of self-organization is remarkable for allowing robust and spontaneous communication of direction over large distances within cell layers. It demonstrates one way in which coordinated behavior can arise in our bodies helping them to heal and grow.

Institute of Science and Technology Austria

Related Protein Articles from Brightsurf:

The protein dress of a neuron
New method marks proteins and reveals the receptors in which neurons are dressed

Memory protein
When UC Santa Barbara materials scientist Omar Saleh and graduate student Ian Morgan sought to understand the mechanical behaviors of disordered proteins in the lab, they expected that after being stretched, one particular model protein would snap back instantaneously, like a rubber band.

Diets high in protein, particularly plant protein, linked to lower risk of death
Diets high in protein, particularly plant protein, are associated with a lower risk of death from any cause, finds an analysis of the latest evidence published by The BMJ today.

A new understanding of protein movement
A team of UD engineers has uncovered the role of surface diffusion in protein transport, which could aid biopharmaceutical processing.

A new biotinylation enzyme for analyzing protein-protein interactions
Proteins play roles by interacting with various other proteins. Therefore, interaction analysis is an indispensable technique for studying the function of proteins.

Substituting the next-best protein
Children born with Duchenne muscular dystrophy have a mutation in the X-chromosome gene that would normally code for dystrophin, a protein that provides structural integrity to skeletal muscles.

A direct protein-to-protein binding couples cell survival to cell proliferation
The regulators of apoptosis watch over cell replication and the decision to enter the cell cycle.

A protein that controls inflammation
A study by the research team of Prof. Geert van Loo (VIB-UGent Center for Inflammation Research) has unraveled a critical molecular mechanism behind autoimmune and inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis.

Resurrecting ancient protein partners reveals origin of protein regulation
After reconstructing the ancient forms of two cellular proteins, scientists discovered the earliest known instance of a complex form of protein regulation.

Sensing protein wellbeing
The folding state of the proteins in live cells often reflect the cell's general health.

Read More: Protein News and Protein Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.