| Date | 17th, Jul 2022 |
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Protein function and activity are determined by both their assembly and secondary structure. Abnormalities related to either protein aggregation or secondary structure can lead to neurodegenerative diseases.
In a new study, an international research team reveals how fluoride nanoparticles, materials used in in vivo imaging, affect the assembly and structure of the amyloid ? protein. Their results present a step towards better treatment and prevention of neurologic disorders like Alzheimer’s disease.
Self-assembly, or the association of individual units of a material into ordered structures or patterns, is a phenomenon of great research interest for materials scientists. One prominent example of self-assembly comes from the self-assembly of proteins in biological systems. Their assembly state governs the function and activity of proteins. Additionally, the protein’s “secondary structure,” characterized by its folding into structures, such as a ?-sheet, also plays a role. Abnormalities in the protein secondary structures or their assembly can lead to various neurodegenerative diseases, including Alzheimer’s.
Nanoparticles (NPs) offer a promising route for treating and preventing such diseases by allowing a controlled and targeted drug delivery. Additionally, inorganic NPs, such as fluoride NPs, are used in brain imaging applications. Compared to organic NPs, inorganic NPs are considered a better candidate for developing high functional materials. But, there is much concern regarding their bio-toxicity. While their interactions with bioproteins have been studied, the mechanism underlying these interactions are not well understood.
An international team of scientists from Tokyo University of Science (TUS) in Japan and Nazarbayev University in Kazakhstan has addressed this issue. In their study, which was made available online on June 2, 2022, and was published in Volume 5, Issue 6 the journal ACS Applied Bio Materials, 2022, the team investigated a section of the amyloid ? peptide (a protein found in the plaques forming in the brains of patients with Alzheimer’s disease) in solution with fluoride ceramic (CeF3) NPs.
Junior Associate Professor Masakazu Umezawa led the study. It included contributions from Mr. Naoya Sakaguchi from TUS and Assistant Professors Mehdi Amouei Torkmahalleh and Dhawal Shah from Nazarbayev University.
The team used a technique called “Fourier transform infrared spectroscopy” (FTIR) to directly monitor the effect of the NP surface on the peptide bonds. “We found that, near the nanoparticle surface, peptides are more likely to form ?-sheets. This comes as an effect of hydrophobicity. The peptide parts that are repelled by the water solution stick to the nanoparticles, and form aggregates more easily,” explains Dr. Umezawa.
In addition, the team investigated the effect of other surrounding ions in the solution. “What we found was very surprising. Even without the nanoparticles, the environment affected the rate of secondary structure formation,” says Dr. Umezawa, “This effect, resulting from a combination of electrostatic interaction and hydrogen bonding, was exaggerated upon adding nanoparticles. The ?-sheet formation can be either suppressed or promoted with a careful choice of ions and nanoparticles. This implies that the process can be controlled and engineered to eradicate adverse effects.”
