Aβ-AMYLOID FIBRILS ARE SELF-TRIGGERED BY THE INTERFACIAL LIPID ENVIRONMENT AND LOW PEPTIDE CONTENT.

We studied the surface properties of Aβ(1-40) amyloid peptide mixed with POPC (liquid state) or DSPC (solid state) phospholipids by using nano-structured lipid/peptide films (Langmuir monolayers). Pure Aβ(1-40) amyloid peptide forms 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 peptide content. At low Aβ(1-40) amyloid peptide proportion (from 2.5 % to 10 % of peptide area proportion) we observed the formation of fibril-like structure when mixed only with POPC lipid. 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 nano-structured fibrils are Thioflavin T positive when observed with fluorescence microscopy. The amyloid fibril network at the surface was also evidenced by Atomic Force Microscopy when the films are transferred onto mica support. Aβ(1-40) amyloid mixed with the solid DSPC lipid showed an immiscible behavior in all peptide proportions without fibrils 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, i.e. the physical state of the water-lipid interface and the relative content of amyloid protein present at the interface.