Gangliosides smelt nanostructured amyloid Aβ(1−40) fibrils in a membrane lipid Environment

BOLAÑO ALVAREZ, ALAIN,; RODRIGUEZ, PABLO E., ; FIDELIO G.D.

CABA (Forma virtual)

Congreso; XLIX Reunión Anual de la Sociedad Argentina de Biofísica; 2021

Sociedad Argentina de Biofisica

Gangliosides induced a smelting process in nanostructuredamyloid fibril-like films throughout the surface properties contributed by glycosphingolipidswhen mixed with 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC)/Aβ(1−40) amyloid peptide. We observed adynamical smelting process when pre-formed amyloid/phospholipid mixture islaterally mixed with gangliosides. This particular environment,gangliosides/phospholipid/Aβ(1−40)peptide mixed interfaces, shown complex miscibility behavior depending ongangliosides content. At 0 % of ganglioside covered surface respect to POPC, Aβ(1−40) peptide forms fibril-likestructure. In between 5-15 % of gangliosides, the fibrils dissolve intoirregular domains and they disappear when the proportion of gangliosides reachthe 20%. The amyloid interfacial dissolving effect of gangliosides is takenplace at lateral pressure equivalent to the organization of biologicalmembranes. The domains from the monolayers are clearly evidenced by usingBrewster Angle Microscopy and Atomic Force Microscopy when the films aretransferred onto a mica support. The domains are Thioflavin T (ThT) positivewhen observed by fluorescence microscopy. We postulated that the smeltingprocess of amyloids fibrils-like structure at the membrane surface provoked bygangliosides is a direct result of the interfacial properties and a newinterfacial environment imposed by the complex glycosphingolipids. We addexperimental evidence, for the first time, how a change in the lipidenvironment (increase in ganglioside proportion) induces a rapid loss of theasymmetric structure of amyloid fibrils by a simple modification of themembrane condition (a more physiological situation).(Thepresent report was recently published in BBA at doi.org/10.1016/j.bbamem.2021.183749special issue dedicated to Professor Félix M. Goñi, on occasion of his 70thbirthday)