The reverse sequence of Aβ amyloid self-triggers isolated nano-fibers and oligomers in lipid environment

Nanostructured lipid/peptide film at air/water interface allow to build different molecular arrangements depending of peptide sequence, peptide proportion and type of lipid. We studied the surface properties of Aβ(1 −42) and its retro-isomer Aβ(42 −1) amyloid peptides mixed with 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) lipid at the air/water interface. In absence of lipids, pure form of both Aβ(1 −42) and Aβ(42 −1) form insoluble monolayer films without appreciable fibril-like structures despite the high interfacial confinement. We show the lipid/peptide interfacial organization depends on the reversing sequence peptide in lipid enriched environment. In POPC/Aβ(1 −42) mixed film we have observed network fibril-like structures. However, using Aβ(42 −1) retro-isomer peptide to form the mixed film, the induced structuration acquired an isolated fibers arrangement associated with oligomers. The above structures are clearly visualized at the interface by using Brewster Angle Microscopy. In the same way, the isolate fibers and oligomers become Thioflavin T positive when they are observed by Fluorescence Microscopy. Thus, we attributed an amyloid behavior at the air/water interface that was also evidenced by Scanning Electron Microscopy when the mixed film was transferred to mica support. Changes from an exclusive β-sheet in pure peptide to a notable increase in α-helix/unordered conformations were induced by the presence of the lipid keeping with fibril-like structures. We postulated that the amyloid fibril formation at the membrane interface not only depends on the interfacial lipid environment and the low amyloid peptide content but also by the reversing sequencing that imposed a differential lipid/peptide interaction at the interface. Despite the retro-isomer peptide has not impact nor the overall molecular hydrophobicity neither on the interfacial behavior although perform a “conformational selective process” that depends on the β-sheet and α-helix contents.