title: Amyloid-β peptides in interaction with raft-mime model membranes: a neutron reflectivity insight.
abstract: The role of first-stage β-amyloid aggregation in the development of the Alzheimer disease, is widely accepted but still unclear. Intimate interaction with the cell membrane is invoked. We designed Neutron Reflectometry experiments to reveal the existence and extent of the interaction between β-amyloid (Aβ) peptides and a lone customized biomimetic membrane, and their dependence on the aggregation state of the peptide. The membrane, asymmetrically containing phospholipids, GM1 and cholesterol in biosimilar proportion, is a model for a raft, a putative site for amyloid-cell membrane interaction. We found that the structured-oligomer of Aβ(1-42), its most acknowledged membrane-active state, is embedded as such into the external leaflet of the membrane. Conversely, the Aβ(1-42) unstructured early-oligomers deeply penetrate the membrane, likely mimicking the interaction at neuronal cell surfaces, when the Aβ(1-42) is cleaved from APP protein and the membrane constitutes a template for its further structural evolution. Moreover, the smaller Aβ(1-6) fragment, the N-terminal portion of Aβ, was also used. Aβ N-terminal is usually considered as involved in oligomer stabilization but not in the peptide-membrane interaction. Instead, it was seen to remove lipids from the bilayer, thus suggesting its role, once in the whole peptide, in membrane leakage, favouring peptide recruitment.
authors.affiliation: Dept. of Medical Biotechnologies and Traslational Medicine, University of Milano, LITA, Via F.lli Cervi, 93. 20090 Segrate (Milano), Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Rondelli
authors.affiliation: Dept. of Medical Biotechnologies and Traslational Medicine, University of Milano, LITA, Via F.lli Cervi, 93. 20090 Segrate (Milano), Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Brocca
authors.affiliation: Dept. of Medical Biotechnologies and Traslational Medicine, University of Milano, LITA, Via F.lli Cervi, 93. 20090 Segrate (Milano), Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Motta
authors.affiliation: Dept. of Molecular Biochemistry and Pharmacology, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20156 Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Messa
authors.affiliation: Dept. of Molecular Biochemistry and Pharmacology, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20156 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Colombo
authors.affiliation: Dept. of Molecular Biochemistry and Pharmacology, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20156 Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.affiliation: Institut Laue-Langevin, 71 avenue des Martyrs, BP 156, 38000 Grenoble Cedex, France.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Fragneto
authors.affiliation: Dept. of Medical Biotechnologies and Traslational Medicine, University of Milano, LITA, Via F.lli Cervi, 93. 20090 Segrate (Milano), Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cantù
authors.affiliation: Dept. of Medical Biotechnologies and Traslational Medicine, University of Milano, LITA, Via F.lli Cervi, 93. 20090 Segrate (Milano), Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Del Favero
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D000067558:Biological Mimicry; D032701:Biomimetics; D002462:Cell Membrane; D016537:Gangliosidosis, GM1 / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers; D009502:Neutrons; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers