| Abstract |
Alzheimer s disease is characterized by the presence of amyloid plaques in the brain. The main components of these plaques are the A beta(1-40) and A beta(1-42) peptides but the A beta(25-35) sequence is the most frequently studied fragment because it represents a biologically active region of the longer A beta peptides. In the present work, the interactions of A beta(25-35) peptide with model membranes were investigated, taking into consideration the aggregation state of the peptide. Monolayers and liposomes were taken as model membranes with two lipid compositions: the equimolar ternary mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM), and cholesterol (Chol) and the equimolar POPC/SM binary mixture. The interaction of A beta(25-35) with the monolayers, investigated at low concentrations (0.25-4 mu M), suggested a three step mechanism: adsorption monomers or dimers adsorb at the polar region of the lipid monolayer; nucleation adsorbed peptides act as nucleation sites for higher aggregates; and penetration these aggregates insert in the hydrophobic region of the monolayer. Chol slightly enhances the peptide-lipid monolayer interaction. The large aggregates nucleated in the bulk solution evidenced a weak interaction with monolayers. The interaction of A beta(25-35) with liposomes, followed by a Quartz Crystal Microbalance with Dissipation (QCM-D) in a large range of peptide concentrations (10-80 mu M), was very small, independently of the peptide concentration. (C) 2016 Elsevier B.V. All rights reserved. |
