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ILL - From neutrons to neurons
Like a synchrotron's X-rays, neutron beams reveal the structure of inert matter, but now biologists too are making increasing use of the research infrastructure in Grenoble to study the complex molecules that make up living matter. Very specialised work carried out in partnership between the Institut Laue-Langevin (ILL) and the European Synchroton Radiation Facility (ESRF) relates specifically to neural cell adhesion molecules (known by the acronym NCAM), which are responsible for rejection or adhesion between nerve cells in the synapses.This research underpins major challenges at a medical level. If the purpose of the adhesion mechanisms in these long molecules attached to the cell membrane is to ensure the stability and integrity of connections between neurons, then repulsion mechanisms, on the other hand, are in charge of the migration of young cells and thus allow for development of the central nervous system.This plasticity, which is essential for its construction, also proves to be crucial for its reconstruction, in terms of therapeutic prospects. Conversely, the migratory phenomenon of neuron cells is also an aggravating factor in brain cancers. From adhesion to repulsion To understand how adhesion and repulsion occur, scientists firstly measured the thickness of adhesion molecules. A monolayer of Neural Cell Adhesion Molecules (NCAMs) was deposited on a film, reproducing a cell membrane. Using synchrotron radiation and neutron spectrometers at the ILL and the ESRF, researchers have confirmed a result that had already been anticipated: the layer is much thinner than it should be if the seven molecule segments are aligned perpendicular to the membrane. In actual fact, the protein is folded over at a point level with its second segment, thus reducing the adhesion distance between two cells. Neutrons diffracted by the proteins have thus allowed the thickness and roughness of the adhesion layer to be measured and its composition to be determined. Once this information was confirmed, researchers were able to identify, in the adhesion mechanism, the dual role of a polysialic acid (PSA) polymer and the presence of sodium in the cell medium. “Two types of NCAM are present on the neuron membranes,” explains Oleg Konovalov, head of research at the ESRF. “Those associated with young cells have a PSA chain, whereas the others do not. The PSA chain inhibits adhesion by surrounding and masking the areas of the molecule that are involved. We wanted to understand the process known as repulsion, which is essential to allow newly formed cells to migrate and find their place in the nervous system." A question of salinity How do these cells attach themselves when they reach their destination? By determining how far the NCAMs extend over the surface of the cell membrane and measuring the space occupied by the polymer, researchers have been able to answer this question. “Normally, PSA prevents adhesion. But, by increasing the salinity, the polymer retracts and allows areas of the molecule to show through, ensuring the adhesion mechanism. The protein then becomes adhesive again. It is by affecting the salinity of the medium that cellular adhesion is controlled,” says Giovanna Fragneto, a specialist in cell membranes at the ILL. This recent research into NCAMs does not yet allow for direct applications. The knowledge relating to cell adhesion mechanisms and the proteins involved nevertheless appears to affor interesting prospects for the future. The research could result in treatments for neurodegenerative illnesses, such as Alzheimer's disease, or a way to control the growth of hippocampus cells on artificial structures in order to provide care for spinal cord lesions. Certain bio-engineers hope to find clues to joining biological material and artificial prostheses. Others, conversely, dream of integrating nerve tissue within electronic equipment, to construct “biological” computers. Through observation of matter and life, work carried out at the ILL and the ESRF at Grenoble's “Scientific Polygon” site serves first of all to remind us that the basis for all scientific research is the observation of nature. It is only on this basis that laws and theories are constructed and validated. Whether based on neutrons, X-rays or electron microscopy, modern investigation techniques provide scientists with observation facilities unequalled in history. At the same time, with our knowledge increasing all the time thanks to these tools, the discoveries they allow give rise to as many questions as answers… |