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Updated: Jan 15, 2026
Characterization of pH-Dependent Reversible Self-Assembly of Amyloid Beta 1-40-Coated Gold Colloids
Published on: March 21, 2025
pH modulates amyloid-β42 conformation in lipid membranes: evidence from circular dichroism, Raman spectroscopy, and
Khlood A A Abdeljawaad1,2,3, Yersultan Arynbek1,4,5, Kahramon Mamatkulov1
1Frank Laboratory of Neutron Physics, Department of Raman Spectroscopy, Joint Institute for Nuclear Research, Dubna, Russia.
Abstract:
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.
Insights
pH significantly alters amyloid-beta42 (Aβ42) structure in neuronal membranes. Acidic conditions promote alpha-helical forms, while neutral and alkaline pH favor random-coil structures, impacting Alzheimer's disease progression.
Area of Science:
- Neuroscience
- Biochemistry
- Membrane Biophysics
Background:
- Alzheimer's disease (AD) pathogenesis involves amyloid-beta42 (Aβ42) conformational changes within neuronal membranes.
- Understanding Aβ42 structural dynamics in lipid bilayers is crucial for elucidating AD mechanisms.
Purpose of the Study:
- To investigate the impact of varying pH levels on the conformation of Aβ42 peptides within model neuronal membranes.
- To elucidate the role of pH in modulating Aβ42 structural transitions and potential aggregation.
Main Methods:
- Utilized Raman spectroscopy and circular dichroism (CD) for experimental structural analysis.
- Employed molecular dynamics (MD) simulations to complement experimental findings and probe membrane interactions.
- Examined Aβ42 conformation in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayers across a range of pH values (5.5, 7.4, 9.5).
Main Results:
- Aβ42 exhibited a pH-dependent conformational shift, favoring α-helical structures at acidic pH (5.5) and increasing random-coil structures at neutral (7.4) and alkaline (9.5) pH.
- Minimal β-sheet content was observed across all pH conditions, though MD simulations suggested transient β-bridge contacts indicative of early aggregation.
- MD simulations indicated minor pH-dependent alterations in DPPC bilayer thickness and lipid order.
Conclusions:
- pH is a critical factor influencing Aβ42 structural dynamics within neuronal membranes.
- These pH-mediated conformational changes offer mechanistic insights into Aβ42 neurotoxicity in Alzheimer's disease.
- Findings provide a basis for developing pH-targeting therapeutic strategies for Alzheimer's disease.
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