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.
Amyloidβ Peptides in interaction with raft-mime model membranes : a neutron reflectivity insight / V. Rondelli, P. Brocca, S. Motta, M. Messa, L. Colombo, M. Salmona, G. Fragneto, L. Cantu, E. Del Favero. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 6(2016 Feb 16), pp. 20997.1-20997.11.
|Titolo:||Amyloidβ Peptides in interaction with raft-mime model membranes : a neutron reflectivity insight|
RONDELLI, VALERIA MARIA (Primo)
BROCCA, PAOLA (Secondo)
CANTU', LAURA FRANCA (Corresponding)
DEL FAVERO, ELENA (Ultimo)
|Settore Scientifico Disciplinare:||Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)|
|Data di pubblicazione:||16-feb-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/srep20997|
|Appare nelle tipologie:||01 - Articolo su periodico|