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Issue 13, 2016
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Amyloid-β25–35 peptides aggregate into cross-β sheets in unsaturated anionic lipid membranes at high peptide concentrations

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Abstract

One of the hallmarks of Alzheimer's disease is the formation of protein plaques in the brain, which mainly consist of amyloid-β peptides of different lengths. While the role of these plaques in the pathology of the disease is not clear, the mechanism behind peptide aggregation is a topic of intense research and discussion. Because of their simplicity, synthetic membranes are promising model systems to identify the elementary processes involved. We prepared unsaturated zwitterionic/anionic lipid membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-phosphocholine (POPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) at concentrations of POPC/3 mol% DMPS containing 0 mol%, 3 mol%, 10 mol%, and 20 mol% amyloid-β25–35 peptides. Membrane-embedded peptide clusters were observed at peptide concentrations of 10 and 20 mol% with a typical cluster size of ∼11 μm. Cluster density increased with peptide concentration from 59 (±3) clusters per mm2 to 920 (±64) clusters per mm2, respectively. While monomeric peptides take an α-helical state when embedded in lipid bilayers at low peptide concentrations, the peptides in peptide clusters were found to form cross-β sheets and showed the characteristic pattern in X-ray experiments. The presence of the peptides was accompanied by an elastic distortion of the bilayers, which can induce a long range interaction between the peptides. The experimentally observed cluster patterns agree well with Monte Carlo simulations of long-range interacting peptides. This interaction may be the fundamental process behind cross-β sheet formation in membranes and these sheets may serve as seeds for further growth into amyloid fibrils.

Graphical abstract: Amyloid-β25–35 peptides aggregate into cross-β sheets in unsaturated anionic lipid membranes at high peptide concentrations

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Publication details

The article was received on 22 Oct 2015, accepted on 07 Feb 2016 and first published on 08 Feb 2016


Article type: Paper
DOI: 10.1039/C5SM02619A
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Soft Matter, 2016,12, 3165-3176
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    Amyloid-β25–35 peptides aggregate into cross-β sheets in unsaturated anionic lipid membranes at high peptide concentrations

    J. Tang, R. J. Alsop, M. Backholm, H. Dies, A. Shi and M. C. Rheinstädter, Soft Matter, 2016, 12, 3165
    DOI: 10.1039/C5SM02619A

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

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      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
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      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
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      [Original citation] - Published by The Royal Society of Chemistry.

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