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Surface behaviour and lipid interaction of Alzheimer beta-amyloid peptide 1-42: a membrane-disrupting peptide

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journal contribution
posted on 2005-01-01, 00:00 authored by E Ambroggio, D Kim, F Separovic, Colin BarrowColin Barrow, K Barnham, L Bagatolli, G Fidelio
Amyloid aggregates, found in patients that suffer from Alzheimer's disease, are composed of fibril-forming peptides in a β-sheet conformation. One of the most abundant components in amyloid aggregates is the β-amyloid peptide 1–42 (Aβ 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 Aβ 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 Aβ 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, Aβ 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 Aβ 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.

History

Journal

Biophysical journal

Volume

88

Issue

4

Pagination

2706 - 2713

Publisher

Biophysical Society

Location

Bethesda, Md.

ISSN

0006-3495

eISSN

1542-0086

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2005, Elsevier

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