Photon and neutron-based techniques for studying membrane dynamics and protein aggregation in lipid–protein interactions

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Submitted: 25.10.2024; Accepted: 25.12.2024; Published 27.12.2024;
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How to Cite

K. Z.  Mamatkulov, H. A.  Esawii, G. M. Arzumanyan. "Photon and neutron-based techniques for studying membrane dynamics and protein aggregation in lipid–protein interactions" Natural Sci. Rev. 1 7 (2024)
https://doi.org/10.54546/NaturalSciRev.100107
K. Z.  Mamatkulov1, H. A.  Esawii1,2,3, G. M. Arzumanyan1,a
  • 1Department of Raman Spectroscopy, Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna, Russia
  • 2Department of Biophysics, Faculty of Science, Cairo University, Giza, Egypt
  • 3Academy of Scientific Research and Technology (ASRT), Cairo, Egypt
  • aarzuman@jinr.ru
DOI: 10.54546/NaturalSciRev.100107
Keywords: lipid–protein interactions, neurodegenerative diseases, amyloid-β, protein aggregation, protein secondary structure, SERS, CARS, SANS , MD simulation
Topics: Physics , Life Sciences , Interdisciplinary Research
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Abstract

Lipid–protein interactions are central to maintaining the structural and functional balance of biological membranes, influencing a wide array of cellular processes. These interactions, however, become pathological in neurodegenerative diseases (NDDs), such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. In these disorders, the misfolding and aggregation of proteins like amyloid-beta (Aβ), alphasynuclein (α-syn), and mutant huntingtin (mHTT) disrupt the lipid bilayer, compromising membrane integrity, fluidity, and signaling. In this review we explore the critical role of lipid–protein interactions in NDDs, emphasizing how protein misfolding leads to toxic aggregates that embed into membranes, triggering neurotoxic events. Advanced spectroscopic techniques have been instrumental in studying these molecular interactions. Photon-based methods, including Förster resonance energy transfer (FRET), circular dichroism (CD), and Raman spectroscopy, provide real-time insights into protein aggregation and lipid membrane dynamics. Neutron-based techniques, such as neutron reflectometry and small-angle neutron scattering (SANS), further enhance the resolution of lipid–protein interactions, particularly in the context of neurodegenerative aggregation.
Moreover, the review highlights the significance of lipid microdomains, particularly cholesterol-rich lipid rafts, which act as platforms for protein aggregation, influencing disease progression. Therapeutic strategies aimed at targeting these lipid–protein interfaces are also discussed, with a focus on how spectroscopic insights have driven the development of drugs that stabilize membrane integrity or prevent toxic aggregation. Finally, the integration of spectroscopy with computational models, such as molecular dynamics (MD) simulations, is proposed as a promising approach to further unravel the complex dynamics of lipid–protein interactions, providing a more complete picture of disease mechanisms.

Acknowledgements

The authors of the article welcome the establishment of a new multidisciplinary scientificjournal NSR at JINR with open access. This journal facilitates the publication of both reviewand original scientific papers, encompassing a broad spectrum of fundamental and practicalresearch conducted within the JINR Member States and worldwide.

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