- 04/05/2021 at 10:35 AM #36674Anonymous UserParticipant
Healing under the magnifying glass of physics
The of is interested in the way in which the interfaces of substances interact with each other and in the way in which they adapt to the constraints undergone. But can physical models help to understand these same issues in living organisms, such as cells? Physicists from (UNIGE), in collaboration with (UZH), used tools of to study the healing process – two cell fronts that come together to heal one . Their study made it possible to identify the scales during which strong interactions appear between cells.
The results, published in the journal , will allow a better analysis of the behavior of the cell fronts, both for healing and for the development of . In the future, this could help to classify cancers and better adapt their treatments, but also to identify new pharmacological targets for transplantation.
By focusing on macroscopic mechanisms, the physics allows you to extract from a consequent of a d’ systems and their mechanisms, regardless of their specific microscopic character. Applied to biological elements, such as the cell fronts bordering a wound, this methodology would make it possible to identify the various interactions involved in the growth and healing processes of tissues, but above all to highlight their hierarchy at the different scales observed.
Patrycja Paruch, Professor in the Department of Physics of quantum of the Faculty of Sciences of the UNIGE, explains: “For the invasion of a cancerous tumor, or in the event of injury, the proliferation of the cell front is crucial, but the and the morphology of this front are very variable. However, we believe that only a few dominant interactions during this process will define the and the shape – smooth or rough, for example – of the front of the cell colony. Experimental observations on several scales of to extract general behaviors can allow us to identify these interactions in healthy tissue and diagnose at what level pathological changes may occur to help combat them. This is where statistical physics comes in. ”
Scarring observed in all its forms
For this multidisciplinary study, the physicists from UNIGE collaborated with the team of Professor Steven Brown from UZH. They used rat epithelial cells flat colonies (2D). Placed in boxes, the cells develop of an insert in removable. When removed by researchers, the cell fronts spread to fill the left by the insert and heal the tissue. “We have reproduced five possible scenarios by ‘handicapping’ the cells in different ways, in order to see what impact this has on the healing process, that is to say on the speed and roughness of the cell front”, specifies Guillaume Rapin, in Patrycja Paruch’s team.
The idea is to see what happens in normal, when the cell phone is blocked, when the between neighboring cells is blocked, when cell mobility is reduced or when cells are continuously over-stimulated. “We took some 300 images per cell front, all four for about 80 hours, which enabled us to observe the mechanisms at very varied scales “, continues Guillaume Rapin.” By applying high performance calculation techniques, we were able to compare our experimental observations with the results of numerical simulations “, adds Nirvana Caballero, researcher in Patrycja Paruch’s team.
Zoom out to see the differences
Scientists have mainly focused on two levels of: within 15 micrometers, below the size of a cell, and between 80 and 200 micrometers, when several cells come into play. “We analyzed how the roughness changes over time to reach its natural dynamic balance, depending on the pharmaco-chemical conditions that we have imposed on the cells, and how this roughness increases depending on the scale at which we look, underlines Nirvana Caballero. In a system with a single hierarchy of mechanism, one would expect to observe the same exponent of roughness at all scales. Here, we see a changing roughness if we look at the scale of a cell or ten cells. “
The Geneva and Zurich teams thus observed only minor variations in roughness below 15 micrometers, whatever the conditions imposed on the cell fronts. On the other hand, between 80 and 150 micrometers, the roughness is altered by the pharmacochemical conditions imposed, reducing the roughness exponent significantly for all non-standard conditions. In addition, the speed of front propagation varied greatly between pharmacochemical conditions: it was slowed down when cell division and mobility were blocked, and accelerated when cells were over-stimulated. “More surprisingly, the fastest healing speed is achieved when certain specific communications between cells are blocked,” notes Guillaume Rapin. This suggests that these communications may be targeted in future therapies, either to promote healing of burns or wounds, or to slow the invasion of cancerous tumors.
These results demonstrate that the interactions at scale play a primary role in the standard process of of a cell front. “We now know at what scale biologists must observe the problematic behaviors of cell fronts, which can lead to the development of tumors,” says Nirvana Caballero. Scientists will now be able to focus on these key scales to probe the fronts of tumor cells and directly compare their pathological interactions with those of healthy cells.
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