Aβ-amyloid fibers drastically alter the topography and mechanical properties of lipid membranes

ALAIN BOLAÑO; PABLO RODRIGUEZ; GERARDO D FIDELIO; BENJAMÍN CARUSO *

LANGMUIR

AMER CHEMICAL SOC

Lugar: Washington; Año: 2023 vol. 39 p. 18923 - 18934

0743-7463

Alzheimer´s disease (AD) is related to the fibrillation of the Aβ peptides at neuronal membranes, a process that depends on the lipid composition, which may impart different physical states to the membrane. In the present work, we study the properties of 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 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 mostly 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 inexistent 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.