Waking up our regenerative pathways Many cells in the body respond to mechanical stimuli by activating different types of signalling pathways, which then affects cell behaviour. We spoke to Dr Moros about the work of the Sirocco project in developing functionalised magnetic nanoparticles to manipulate these pathways, which could open up the possibility of enhancing wound healing and directing stem cell fate. Many of the
cells in our body sense mechanical stimuli, which they then respond to in different ways, for example by proliferating or differentiating. In order to maintain correct blood pressure endothelial cells sense the current situation and then respond accordingly. “When they sense pressure on the surface of the cells, they respond by activating different pathways. They may need to change the contraction or relaxation of cells, finally increasing or decreasing the arterial diameter,” explains Dr María Moros, Principal Investigator of the Sirocco project. A deeper understanding of how cells convert these mechanical stimuli into biochemical activity – a process called mechanotransduction – could open up interesting new therapeutic avenues, a topic that Dr Moros is investigating in the Sirocco project. “In the project we’re looking at wound healing on the skin, which is a relatively simple model,” she says. “If it works, we can then look at other structures, like the heart, liver and intestine.” This could represent a way to essentially activate regeneration pathways which have become dormant in humans over the course of evolutionary history. Some invertebrates are able to fully regenerate themselves, such as the fresh water Hydra vulgaris, but humans do not have the same capacity. “It is not that we don’t have these regenerative pathways, it’s more like they are asleep or are only activated on very specific occasions. These pathways are really active in some of our organs like the intestine – but in other tissues, they are nearly inactive,” says Dr Moros. The wider aim in the project is to provide researchers with a tool to study these pathways and to activate them artificially, which could in the long-term open up the possibility of controlling them in a spatiotemporal way and applying them in regenerative medicine. “These pathways are really powerful in regeneration,” outlines Dr Moros.
Magnetic nanoparticles A specific regeneration pathway which is known to ultimately lead to cell division has been chosen in the project, with researchers now looking to investigate how stimuli are
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Fluorescence microscopy image showing magnetic particles (in red) attached to MDCK cells membranes expressing E-cadherin (in green). Nuclei are stained in blue.
Above image - TEM MNPs: Transmission Electron Microscopy Image of magnetic nanoparticles synthesized for the project.
It is not that we don’t have these regenerative pathways, it’s more like they are “asleep”. We want to be able to activate these pathways when and where we want, so we can get this spatio-temporal control that is difficult to achieve in vivo with other techniques. turned into biochemical signals, using in vitro models of the skin. It’s important to tightly control this process and avoid excessive cell division and protect other areas of the body. “We aim to strike the right balance. We need to activate this pathway, but only when we want and where we want,” stresses Dr Moros. Researchers are investigating how to specifically activate this pathway using magnetic nanoparticles, which Dr Moros says represents a highly novel approach. “We are using magnetic nanoparticles, which can be
activated by stimulating them. So even if the nanoparticles go to other parts of the body, the effect will be localised,” she outlines. “We will be able to activate these pathways when and where we want, so we can get this spatiotemporal control that is difficult to achieve with other techniques.” The magnetic nanoparticles are modified with fragments of cadherins, proteins found on the surface of cells which are responsible for attachment to other cells. The nature of the cadherins depends on the type of cell. “For
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