Quasielastic Neutron Scattering in the Studies on Serious Diseases

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 7005

Special Issue Editor


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Guest Editor
Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, Japan
Interests: neutron scattering; X-ray scattering; quasielastic neutron scattering; small-angle scattering; amyloid; intrinsically disordered proteins; protein dynamics; cardiac muscle

Special Issue Information

Dear colleagues,

Diseases, which often appear as damage at the tissue level, arise due to failures of the underlying systems of related protein networks. The key protein(s) in these systems may fail to be expressed properly, or may exhibit abnormal functions due either to mutation or improper modifications and environments. In order to understand ultimately how the diseases develop, it is necessary to understand these systems at the molecular level. Thus, the physicochemical properties of the related proteins and other possible components involved with the systems need to be investigated. In particular, since it is well recognized that the dynamics of the biological macromolecules play important roles in their functions, the dynamic properties need to be investigated, along with their structures.

Quasielastic neutron scattering (QENS) is a technique that can directly measure the dynamics of biological macromolecules at pico- to nanosecond temporal and subnano- to nanometer spatial scales. As there are no particular sample requirements, this unique technique has been applied to various systems, including protein powders and solutions, and even to living cells and tissues. QENS is, thus, suitable for investigating how the dynamics of disease-related molecules are involved with the pathogenesis of the diseases and how these dynamics are modified under pathological states. The insights obtained from the QENS measurements could provide significant contributions to help elucidate the pathogenic mechanisms of diseases and could help develop therapeutic strategies.

This Special Issue explores how the QENS techniques are applied in studying the molecular mechanisms of the diseases. Topics will include QENS studies on disease-related proteins and other biological macromolecules, tissues and cells in pathological states, and the effects of drugs on the dynamic states of these molecules and cells. This Special Issue will hopefully provide readers with a comprehensive view of the possible applications of QENS in studies on serious diseases.

Dr. Satoru Fujiwara
Guest Editor

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Keywords

  • quasielastic neutron scattering
  • disease
  • molecular mechanism of pathogenesis
  • protein dynamics
  • water dynamics
  • lipid dynamics
  • amyloid

Published Papers (3 papers)

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Research

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14 pages, 3935 KiB  
Article
Dynamical Behavior of Disordered Regions in Disease-Related Proteins Revealed by Quasielastic Neutron Scattering
by Satoru Fujiwara
Medicina 2022, 58(6), 795; https://doi.org/10.3390/medicina58060795 - 13 Jun 2022
Cited by 1 | Viewed by 1572
Abstract
Background and Objectives: Intrinsically disordered proteins (IDPs) and proteins containing intrinsically disordered regions (IDRs) are known to be involved in various human diseases. Since the IDPs/IDRs are fluctuating between many structural substrates, the dynamical behavior of the disease-related IDPs/IDRs needs to be [...] Read more.
Background and Objectives: Intrinsically disordered proteins (IDPs) and proteins containing intrinsically disordered regions (IDRs) are known to be involved in various human diseases. Since the IDPs/IDRs are fluctuating between many structural substrates, the dynamical behavior of the disease-related IDPs/IDRs needs to be characterized to elucidate the mechanisms of the pathogenesis of the diseases. As protein motions have a hierarchy ranging from local side-chain motions, through segmental motions of loops or disordered regions, to diffusive motions of entire molecules, segmental motions, as well as local motions, need to be characterized. Materials and Methods: Combined analysis of quasielastic neutron scattering (QENS) spectra with the structural data provides information on both the segmental motions and the local motions of the IDPs/IDRs. Here, this method is applied to re-analyze the QENS spectra of the troponin core domain (Tn-CD), various mutants of which cause the pathogenesis of familial cardiomyopathy (FCM), and α-synuclein (αSyn), amyloid fibril formation of which is closely related to the pathogenesis of Parkinson’s disease, collected in the previous studies. The dynamical behavior of wild-type Tn-CD, FCM-related mutant Tn-CD, and αSyn in the different propensity states for fibril formation is characterized. Results: In the Tn-CD, the behavior of the segmental motions is shown to be different between the wild type and the mutant. This difference is likely to arise from changes in the intramolecular interactions, which are suggested to be related to the functional aberration of the mutant Tn-CD. In αSyn, concerted enhancement of the segmental motions and the local motions is observed with an increased propensity for fibril formation, suggesting the importance of these motions in fibril formation. Conclusions: Characterization of the segmental motions as well as the local motions is thus useful for discussing how the changes in dynamical behavior caused by the disease-related mutations and/or environmental changes could be related to the functional and/or behavioral aberrations of these proteins. Full article
(This article belongs to the Special Issue Quasielastic Neutron Scattering in the Studies on Serious Diseases)
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10 pages, 1084 KiB  
Article
Melting and Re-Freezing Leads to Irreversible Changes in the Morphology and Molecular-Level Dynamics of Pfizer-BioNTech COVID-19 Vaccine
by Eugene Mamontov, Luke L. Daemen, Eric Novak and Matthew B. Stone
Medicina 2021, 57(12), 1343; https://doi.org/10.3390/medicina57121343 - 9 Dec 2021
Cited by 3 | Viewed by 2708
Abstract
Background and Objectives: As an mRNA-based vaccine, the Pfizer-BioNTech COVID-19 vaccine has stringent cold storage requirements to preserve functionality of the mRNA active ingredient. To this end, lipid components of the vaccine formulation play an important role in stabilizing and protecting the [...] Read more.
Background and Objectives: As an mRNA-based vaccine, the Pfizer-BioNTech COVID-19 vaccine has stringent cold storage requirements to preserve functionality of the mRNA active ingredient. To this end, lipid components of the vaccine formulation play an important role in stabilizing and protecting the mRNA molecule for long-term storage. The purpose of the current study was to measure molecular-level dynamics as a function of temperature in the Pfizer-BioNTech COVID-19 vaccine to gain microscopic insight into its thermal stability. Materials and Methods: We used quasielastic and inelastic neutron scattering to probe (1) the vaccine extracted from the manufacturer-supplied vials and (2) unperturbed vaccine in the original manufacturer-supplied vials. The latter measurement was possible due to the high penetrative power of neutrons. Results: Upon warming from the low-temperature frozen state, the vaccine in its original form exhibits two-step melting, indicative of a two-phase morphology. Once the melting is completed (above 0 °C), vaccine re-freezing cannot restore its original two-phase state. This observation is corroborated by the changes in the molecular vibrational spectra. The molecular-level mobility measured in the resulting single-phase state of the re-frozen vaccine greatly exceeds the mobility measured in the original vaccine. Conclusions: Even a brief melting (above 0 °C) leads to an irreversible alteration of the two-phase morphology of the original vaccine formulation. Re-freezing of the vaccine results in a one-phase morphology with much increased molecular-level mobility compared to that in the original vaccine, suggesting irreversible deterioration of the vaccine’s in-storage stability. Neutron scattering can be used to distinguish between the vibrational spectra characteristic of the original and deteriorated vaccines contained in the unperturbed original manufacturer-supplied vials. Full article
(This article belongs to the Special Issue Quasielastic Neutron Scattering in the Studies on Serious Diseases)
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Review

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16 pages, 3318 KiB  
Review
Water Dynamics in Cancer Cells: Lessons from Quasielastic Neutron Scattering
by Murillo L. Martins, Heloisa N. Bordallo and Eugene Mamontov
Medicina 2022, 58(5), 654; https://doi.org/10.3390/medicina58050654 - 12 May 2022
Cited by 4 | Viewed by 2184
Abstract
The severity of the cancer statistics around the globe and the complexity involving the behavior of cancer cells inevitably calls for contributions from multidisciplinary areas of research. As such, materials science became a powerful asset to support biological research in comprehending the macro [...] Read more.
The severity of the cancer statistics around the globe and the complexity involving the behavior of cancer cells inevitably calls for contributions from multidisciplinary areas of research. As such, materials science became a powerful asset to support biological research in comprehending the macro and microscopic behavior of cancer cells and untangling factors that may contribute to their progression or remission. The contributions of cellular water dynamics in this process have always been debated and, in recent years, experimental works performed with Quasielastic neutron scattering (QENS) brought new perspectives to these discussions. In this review, we address these works and highlight the value of QENS in comprehending the role played by water molecules in tumor cells and their response to external agents, particularly chemotherapy drugs. In addition, this paper provides an overview of QENS intended for scientists with different backgrounds and comments on the possibilities to be explored with the next-generation spectrometers under construction. Full article
(This article belongs to the Special Issue Quasielastic Neutron Scattering in the Studies on Serious Diseases)
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