Amyloid-ß(25-35) peptides aggregate into cross-ß sheets in unsaturated anionic lipid membranes at high peptide concentrations.
Soft Matter
; 12(13): 3165-76, 2016 Apr 07.
Article
en En
| MEDLINE
| ID: mdl-26934592
ABSTRACT
One of the hallmarks of Alzheimer's disease is the formation of protein plaques in the brain, which mainly consist of amyloid-ß 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-ß25-35 peptides. Membrane-embedded peptide clusters were observed at peptide concentrations of 10 and 20 mol% with a typical cluster size of â¼11 µm. Cluster density increased with peptide concentration from 59 (±3) clusters per mm(2) to 920 (±64) clusters per mm(2), 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-ß 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-ß sheet formation in membranes and these sheets may serve as seeds for further growth into amyloid fibrils.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
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Péptidos beta-Amiloides
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Membrana Dobles de Lípidos
Tipo de estudio:
Health_economic_evaluation
/
Prognostic_studies
Idioma:
En
Revista:
Soft Matter
Año:
2016
Tipo del documento:
Article
País de afiliación:
Canadá