Physics Perspective on Wound Healing

Credit: Université de Genève

In condensed matter physics, understanding how systems interact between the interfaces that separate them is a central concern. But can physical models clarify similar concepts in biological systems such as cells? Physicists at the University of Geneva (UNIGE), in collaboration with the University of Zurich (UZH), use a chaotic elastic system framework for the process of wound healing, the cell front that eventually binds and closes the lesion. I studied proliferation. Their study identified the scale of dominant interactions between cells that determine this process.Results published in the journal Science reportAllows a better analysis of cell front behavior, both in terms of wound healing and tumorigenesis. In the future, this approach may provide personalized diagnosis to classify cancers, better target their treatments, and identify new pharmacological targets for transplantation.

Statistical physics makes it possible to extract an overview of system behavior independent of specific microscopic characteristics by focusing on the macroscopic characteristics of large datasets. This approach applies to biological factors such as cell fronts adjacent to wounds and makes it possible to identify various interactions that play a decisive role during tissue growth, differentiation, and healing. Above all, it emphasizes those hierarchies on the various scales observed. Professor Patrycja Paruch of the Department of Quantum Materials Physics, Faculty of Science, UNIGE explains: “For cancer tumor infiltration and wounds, cell anterior proliferation is very important, but anterior velocity and morphology are very important, but only a few dominant interactions during this process. We believe that we define the dynamics and shape (eg, smooth or coarse) of the edges of cell colonies, which can be identified by experimental observations over multiple length scales to extract common behavior. These interactions in tissues diagnose at what level pathological changes can occur to help fight them. This is where statistical physics comes in. “

Many scales of wound healing

In this interdisciplinary study, UNIGE physicists collaborated with Professor Steven Brown’s team at UZH. They used rat epithelial cells to establish flat colonies (2D) in which the cells grew around the silicone inserts and then removed them to mimic open lesions. The cell fronts then proliferate, filling the openings and healing the tissue. “We have reproduced five possible scenarios by” handicaping “cells in different ways to see how this affects wound healing, the velocity and roughness of the cell anterior surface. “Guillaume Rapin, a researcher on the Patrycja Paruch team, explains. .. The idea is what happens in normal healthy tissue, when processes such as cell division and communication between adjacent cells are blocked, when cells become less mobile, or when cells are permanently pharmacological. It’s about seeing what happens when you’re stimulated by. “We took about 300 images every 4 hours for about 80 hours, which allowed us to observe the fronts of proliferating cells on a very different scale,” continues Guillaume Rapin. “By applying high-performance computational techniques, we were able to compare the experimental results with the results of numerical simulations,” adds Nirvana Caballero, another researcher on Patrycja Paruch’s team.

Zoom out to increase effectiveness

Scientists have observed two different roughness regimes. It is less than 15 micrometers, which is smaller than the size of one cell, and 80-200 micrometers when multiple cells are involved. “We analyzed how the roughness index changes over time to reach natural dynamic equilibrium, depending on the pharmacochemical conditions imposed on the cells. This roughness is on the scale we see. We analyzed how it would increase accordingly, “emphasizes Nirvana Caballero. “In a system with a single dominant interaction, we expect to see the same roughness index on all scales. Here, when looking at the 1-cell or 10-cell scale, the roughness changes. I understand this.”

The Geneva and Zurich team revealed only slight fluctuations in the roughness index below 15 micrometers, regardless of the conditions imposed on the front of the cell. On the other hand, they found that between 80 and 150 micrometers, the roughness was altered by all pharmacological inhibitors and the roughness index was significantly reduced. In addition, they observed that growth rates differed significantly between different drug-chemical conditions, slowing when cell division and motility were inhibited, and accelerating when cells were stimulated. “More surprisingly, the fastest growth rates were achieved when the gap junction communication between cells was blocked,” says Guillaume Lapin. This observation suggests that such communication may be targeted in future treatments to promote burn or wound healing or to delay infiltration of cancerous tumors.

These results indicate that medium-scale interactions play an important role in determining the healthy growth of cell fronts. “We now know on what scale biologists should look for problematic behaviors on the cellular front that can lead to tumor development,” says Nirvana Caballero. Scientists can now focus on these important length scales to examine the front lines of tumor cells and compare pathological interactions directly with those of healthy cells.

New research reveals how skin cells prepare to heal wounds

For more information:
Guillaume Rapin et al. Roughness and dynamics of proliferating cell fronts as probes of cell-cell interactions, Science report (2021). DOI: 10.1038 / s41598-021-86684-3

Courtesy of the University of Geneva

Quote: The Physics Perspective on Wound Healing (May 3, 2021) was obtained from on May 3, 2021. It was.

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Physics Perspective on Wound Healing

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