Modulation of the phospholipid dynamics and bilayer water accessibility with the membrane-associated nucleation of β-amyloid (Aβ) peptides.

Authors

Brian Lum, Wei Qiang

Published in

Biophysical chemistry. Volume 338. Pages 107693. Jul 31, 2026. Epub Jul 31, 2026.

Abstract

Membrane disruption along the amyloidogenic aggregation of β-amyloid (Aβ) peptides is considered a molecular mechanism for the Aβ-induced cell toxicity and death. Yet, the underlying structural basis for the harmful Aβ-membrane interactions that lead to disruption remains poorly understood. We have been utilizing solid-state nuclear magnetic resonance (ssNMR) spectroscopy to explore the intermediate states of membrane-associated Aβ aggregation, as well as their roles in membrane disruption process. Aligning with this general objective, complementary quantitative ssNMR spectroscopy focusing on the modulation of phospholipid dynamics in membrane bilayers will provide useful insight about how these intermediate states influence the physicochemical properties and architecture of membranes. In the current work, we systematically investigate how specific molecular motions of phospholipids change in the presence of membrane-associated 40- and 42-residue Aβ isoforms, within the time frame of nucleation processes. Physicochemical parameters, including the lipid headgroup and lateral diffusive motion correlation time, the lipid alkyl chain to headgroup ¹H¹H cross relaxation rate, and the H₂O-assisted ¹H¹³C cross polarization rate to lipid alkyl ¹³Cs, were monitored by various ssNMR spectroscopic approaches. The outcomes suggest a general rigidification of bilayers upon instant Aβ-bilayer interactions across different bilayer phospholipid compositions and Aβ isoforms, accompanied by increase of water accessibility to bilayer interiors. These observations, together with the knowledge of molecular structural evolution of Aβ within the same time frame, help to establish a molecular-level, schematic explanation of the membrane-associated Aβ nucleation process.

PMID:
42543041
Bibliographic data and abstract were imported from PubMed on 03 Aug 2026.

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