title: Surface behavior and lipid interaction of Alzheimer beta-amyloid peptide 1-42: a membrane-disrupting peptide.
abstract: Amyloid aggregates, found in patients that suffer from Alzheimer's disease, are composed of fibril-forming peptides in a beta-sheet conformation. One of the most abundant components in amyloid aggregates is the beta-amyloid peptide 1-42 (Abeta 1-42). Membrane alterations may proceed to cell death by either an oxidative stress mechanism, caused by the peptide and synergized by transition metal ions, or through formation of ion channels by peptide interfacial self-aggregation. Here we demonstrate that Langmuir films of Abeta 1-42, either in pure form or mixed with lipids, develop stable monomolecular arrays with a high surface stability. By using micropipette aspiration technique and confocal microscopy we show that Abeta 1-42 induces a strong membrane destabilization in giant unilamellar vesicles composed of palmitoyloleoyl-phosphatidylcholine, sphingomyelin, and cholesterol, lowering the critical tension of vesicle rupture. Additionally, Abeta 1-42 triggers the induction of a sequential leakage of low- and high-molecular-weight markers trapped inside the giant unilamellar vesicles, but preserving the vesicle shape. Consequently, the Abeta 1-42 sequence confers particular molecular properties to the peptide that, in turn, influence supramolecular properties associated to membranes that may result in toxicity, including: 1), an ability of the peptide to strongly associate with the membrane; 2), a reduction of lateral membrane cohesive forces; and 3), a capacity to break the transbilayer gradient and puncture sealed vesicles.
authors.affiliation: CIQUIBIC-CONICET, Departamento de Química Biológica, Facultad de Ciencias Químicas, Ciudad Universitaria, Córdoba CP-5000, Argentina.
authors.forename: Ernesto E
authors.initials: EE
authors.lastname: Ambroggio
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Kim
authors.forename: Frances
authors.initials: F
authors.lastname: Separovic
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Barrow
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Barnham
authors.forename: Luis A
authors.initials: LA
authors.lastname: Bagatolli
authors.forename: Gerardo D
authors.initials: GD
authors.lastname: Fidelio
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001703:Biophysics / Q000379:methods*; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D007477:Ions; D007700:Kinetics; D008051:Lipid Bilayers; D008055:Lipids / Q000737:chemistry*; D018613:Microscopy, Confocal; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D011312:Pressure; D011485:Protein Binding; D013109:Sphingomyelins / Q000737:chemistry; D013499:Surface Properties; D013696:Temperature
chemical_list: D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D007477:Ions; D008051:Lipid Bilayers; D008055:Lipids; D010446:Peptide Fragments; D010455:Peptides; D010713:Phosphatidylcholines; D013109:Sphingomyelins; C075222:amyloid beta-protein (1-42); D002784:Cholesterol