Aβ-amyloid fibrils are self-triggered by the interfacial lipid environment and low peptide content

Abstract

We studied the surface properties of Aβ(1-40) amyloid peptides mixed with 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) (liquid state) or 1,2-disteraoyl-phosphatidylcholine (DSPC) (solid state) phospholipids by using nanostructured lipid/peptide films (Langmuir monolayers). Pure Aβ(1-40) amyloid peptides form insoluble monolayers without forming fibril-like structures. In a lipid environment [phospholipid/Aβ(1-40) peptide mixtures], we observed that both miscibility and stability of the films depend on the peptide content. At low Aβ(1-40) amyloid peptide proportion (from 2.5 to 10% of peptide area proportion), we observed the formation of a fibril-like structure when mixed only with POPC lipids. The stability acquired by these mixed films is within 20-35 mN·m-1 compatible with the equivalent surface pressure postulated for natural biomembranes. Fibrils are clearly evidenced directly from the monolayers by using Brewster angle microscopy. The so-called nanostructured fibrils are thioflavin T positive when observed by fluorescence microscopy. The amyloid fibril network at the surface was also evidenced by atomic force microscopy when the films are transferred onto a mica support. Aβ(1-40) amyloid mixed with the solid DSPC lipid showed an immiscible behavior in all peptide proportions without fibril formation. We postulated that the amyloid fibrillogenesis at the membrane can be dynamically nano-self-triggered at the surface by the quality of the interfacial environment, that is, the physical state of the water-lipid interface and the relative content of amyloid protein present at the interface.