Аңдатпа
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.