Alterations in protein structure and assembly with


image: The effect of CeF3 nanoparticles on the structure of beta-amyloid protein is measured directly by FT-IR spectroscopy. Secondary structure formation appears as a feature in the IR spectrum.
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Credit: Masakazu Umezawa of Tokyo University of Science

Self-assembly, or the association of individual units of a material into ordered structures or patterns, is a phenomenon of great research for materials scientists. A striking example of self-assembly comes from the self-assembly of proteins in biological systems. The function and activity of proteins are governed by their state of assembly. In addition, the “secondary structure” of the protein, characterized by its folding into structures, such as a β-sheet, also plays a role. Indeed, abnormalities in the secondary structures of proteins or their assembly can lead to various neurodegenerative diseases, including Alzheimer’s disease.

Nanoparticles (NPs) offer a promising avenue for the treatment and prevention of such diseases by allowing controlled and targeted drug delivery. Additionally, inorganic NPs, such as fluorinated NPs, are used in brain imaging applications. Compared to organic NPs, inorganic NPs are considered a better candidate for the development of highly functional materials. But, there is much concern about their biotoxicity. Although their interactions with bioproteins have been studied, the mechanism underlying these interactions is not well understood.

An international team of scientists from Tokyo University of Science (TUS) in Japan and Nazarbayev University in Kazakhstan have now looked into this question. In their study, posted online on June 2, 2022 and published in volume 5, number 6, the journal Applied Biological Materials ACS on June 20, 2022, the team investigated a section of the amyloid β peptide (a protein found in the plaques that form in the brains of patients with Alzheimer’s disease) in solution with fluoride ceramic (CeF3) NP. The study was led by Junior Associate Professor Masakazu Umezawa and included contributions from Mr Naoya Sakaguchi of TUS and Assistant Professors Mehdi Amouei Torkmahalleh and Dhawal Shah of Nazarbayev University.

The team used a technique called “Fourier Transform Infrared Spectroscopy” (FTIR) to directly monitor the effect of NP surface on peptide bonds. “We found that near the surface of the nanoparticles, the peptides are more likely to form β-sheets. This comes as an effect of hydrophobicity. The parts of the peptide that are repelled by the aqueous solution adhere to the nanoparticles and more easily form aggregates,” explains Dr. Umezawa.

Additionally, the team studied the effect of other surrounding ions in the solution. “What we discovered is very surprising. Even without the nanoparticles, the environment affected the rate of secondary structure formation,” said Dr. Umezawa“This effect, resulting from a combination of electrostatic interaction and hydrogen bonding, was exaggerated when nanoparticles were added. With a careful choice of ions and nanoparticles, the formation of β-sheets can be suppressed or This implies that the process can be controlled and designed to eradicate undesirable effects.

The experimental results were complemented by molecular dynamics simulations carried out by the team from Nazarbayev University. This, in turn, helped design and guide the experiments as well as provide insight into the results.

With this deeper understanding of the interaction between proteins and NPs, the study paves the way for controlled protein folding processes. With such control, all protein deformations could be eliminated and positive interactions and structural changes could be promoted. This could lead to a better protocol for the prevention and treatment of Alzheimer’s disease and, ultimately, to a better quality of life for the elderly.




About Tokyo University of Science

Tokyo University of Science (TUS) is a well-known and respected university, and the largest private research university specializing in science in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Founded in 1881, the university has continuously contributed to the scientific development of Japan by instilling a love of science in researchers, technicians and educators.

With a mission to “create science and technology for the harmonious development of nature, human beings and society”, TUS has undertaken a wide range of research from basic science to applied science. TUS has taken a multidisciplinary approach to research and undertaken intensive studies in some of today’s most vital areas. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel laureate and the only private university in Asia to produce Nobel laureates within the field of natural sciences.


About Junior Associate Professor Masakazu Umezawa of Tokyo University of Science

Dr. Masakazu Umezawa is currently a Junior Associate Professor at Tokyo University of Science (TUS), Japan. He completed his PhD in Pharmacy and Drug Design in 2010 at TUS and held postdoc and project research associate positions there before becoming a junior associate professor in April 2021. His research interests include the study nano-bio interactions, in particular the structural change and assembly of proteins and lipids on the surface of inorganic and organic nanoparticles in physiological fluids. It aims to promote pharmaceutically effective and safer use of well-designed nanoparticles. Dr. Umezawa has published 100 peer-reviewed articles with over 1900 citations.

Funding Information

This study was funded by Tokyo University of Science: Faculty of Advanced Engineering Young Scientists Collaborative Research Fellowship (2021) and Nazarbayev University: Collaborative Research Project (11022021CRP1503).

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