title: Interaction of the Alzheimer Aβ(25-35) peptide segment with model membranes.
abstract: Alzheimer's disease is characterized by the presence of amyloid plaques in the brain. The main components of these plaques are the Aβ(1-40) and Aβ(1-42) peptides but the Aβ(25-35) sequence is the most frequently studied fragment because it represents a biologically active region of the longer Aβ peptides. In the present work, the interactions of Aβ(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 Aβ(25-35) with the monolayers, investigated at low concentrations (0.25-4μM), 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 Aβ(25-35) with liposomes, followed by a Quartz Crystal Microbalance with Dissipation (QCM-D) in a large range of peptide concentrations (10-80μM), was very small, independently of the peptide concentration.
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Cuco
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; CiiEM, Instituto Superior de Ciências da Saúde Egas Moniz, Campus Universitário, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Serro
authors.affiliation: Centro de Química Física Molecular and IN-Institute of Nanosciences and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: José Paulo
authors.initials: JP
authors.lastname: Farinha
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal. Electronic address: b.saramago@tecnico.ulisboa.pt.
authors.forename: Benilde
authors.initials: B
authors.lastname: Saramago
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal. Electronic address: ameliags@tecnico.ulisboa.pt.
authors.forename: Amélia Gonçalves
authors.initials: AG
authors.lastname: da Silva
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013109:Sphingomyelins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D053835:Unilamellar Liposomes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D008081:Liposomes; D008563:Membrane Lipids; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D013109:Sphingomyelins; D053835:Unilamellar Liposomes; C074636:amyloid beta-protein (25-35); D002784:Cholesterol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; C030345:1,2-dipalmitoylphosphatidylglycerol
keywords: Aβ(25–35) peptide; Cholesterol; Liposomes; Monolayers