Aβ Amyloid Fibers Drastically Alter the Topography and Mechanical Properties of Lipid Membranes

Alain Bolaño Alvarez, Pablo E. A. Rodríguez, Gerardo D. Fidelio*, Benjamín Caruso*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Alzheimer's disease (AD) is related to the fibrillation of the Aβ peptides at neuronal membranes, a process that depends on the lipid composition and may impart different physical states to the membrane. In the present work, we study the properties of the Aβ peptide when mixed with a zwitterionic lipid (DMPC), using the Langmuir monolayer technique as an approach to control membrane physical conditions. First, we build on previous characterizations of pure Aβ monolayers and observe that, in addition to high shear, these films present a pronounced compressional hysteresis. When Aβ is assembled with DMPC in a binary film, the resulting membranes become heterogeneous, with a peptide-enriched phase distributed in a network-like pattern, and they exhibit a lateral transition that depends on the Aβ content. At lower peptide proportions, the films segregate into two well-defined phases: one consisting of lipids and another enriched with peptides. The reflectivity of these phases differs from that obtained for pure Aβ films. Thus, the formed fibers effectively cover most of the interface area and remain stable at higher pressures (from 20 to 30 mN m-1 depending on Aβ content) compared to pure peptide films (17 mN m-1). Furthermore, such structures induce a compressional hysteresis in the film, similar to that of pure peptide films (which is nonexistent in the pure lipid monolayer), even at low peptide proportions. We claim that the mechanical properties at the interface are governed by the size of the fibril-like structures. Based on the low molar fractions and surface packing at which these phenomena were observed, we postulate that as a consequence of peptide intermolecular interactions, Aβ may have drastic effects on the molecular arrangement and mechanical properties of a lipid membrane.

Original languageEnglish
JournalLangmuir
Volume39
Issue number51
Pages (from-to)18923-18934
Number of pages12
ISSN0743-7463
DOIs
Publication statusPublished - 26 Dec 2023

Keywords

  • Humans
  • Amyloid beta-Peptides/chemistry
  • Dimyristoylphosphatidylcholine/chemistry
  • Alzheimer Disease
  • Membranes

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