pH modulates amyloid-β42 conformation in lipid membranes: evidence from circular dichroism, Raman spectroscopy, and molecular dynamics simulations
Abdeljawaad K.A.A. Arynbek Y. Mamatkulov K. Duc Le H. Ibrahim M.A.A. Mekhemer G.A.H. Arzumanyan G.
2025Taylor and Francis Ltd.
Journal of Biomolecular Structure and Dynamics
2025
Alzheimer’s disease (AD) progression is strongly linked to conformational changes of amyloid-β42 (Aβ42) in neuronal membranes. This study examined the influence of pH on Aβ42 conformation in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membranes using Raman spectroscopy, circular dichroism (CD), and molecular dynamics (MD) simulations. At acidic pH (5.5), Aβ42 predominantly adopted α-helical structures (∼75–80%), whereas neutral (pH 7.4) and alkaline conditions (pH 9.5) reduced α-helical content to ∼48–58% and ∼44–47%, respectively, with a corresponding rise in random-coil structures (∼20–36%). Across all pH conditions, β-sheet content remained minimal, although MD trajectories indicated transient β-bridge contacts suggestive of early aggregation. MD analyses revealed modest pH-dependent perturbations in bilayer thickness and lipid order. Consistency across experimental and computational methods highlights pH as a critical modulator of Aβ42 structural dynamics in membranes, providing mechanistic insight into its neurotoxic potential and informing future therapeutic strategies.
Aβ42 , circular dichroism , MD simulations , Raman spectroscopy , secondary structure
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Frank Laboratory of Neutron Physics, Department of Raman Spectroscopy, Joint Institute for Nuclear Research, Dubna, Russian Federation
Academy of Scientific Research & Technology (ASRT), Cairo, Egypt
Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia, Egypt
Faculty of Physics and Technology, Al-Farabi Kazakh National University, Almaty, Kazakhstan
Institute of Nuclear Physics, Almaty, Kazakhstan
Institute of Physics, Vietnam Academy of Science and Technology, Hanoi, Viet Nam
Department of Engineering, College of Engineering and Technology, University of Technology and Applied Sciences, Nizwa, Oman
School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
Frank Laboratory of Neutron Physics
Academy of Scientific Research & Technology (ASRT)
Computational Chemistry Laboratory
Faculty of Physics and Technology
Institute of Nuclear Physics
Institute of Physics
Department of Engineering
School of Health Sciences
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