title: Cholesterol drives aβ(1-42) interaction with lipid rafts in model membranes.
abstract: The molecular mechanism at the basis of the neurodegenerative process related to Alzheimer's disease (AD) is triggered by the local composition of the neural plasma membrane. The role of cholesterol is controversial. In this investigation the interaction of the AD peptide amyloid-beta (1-42) with model membranes containing lipid rafts has been investigated by atomic force microscopy techniques. Supported lipid membranes made of phospholipids/sphingomyelin/cholesterol have been investigated as a function of the molar content of cholesterol, in a range spanning the phase diagram of the lipid system. The administration of amyloid-beta induced a phase reorganization of the lipid domains, when the cholesterol molar fraction was below 5%. At the same time, a mechanical destabilization and an appreciable thinning of the membrane induced by the peptide were detected. The major interaction was observed in the presence of the gel phase Lβ, and was enhanced by a low cholesterol amount. With the appearance of the liquid ordered phase Lo, the effect was hindered. At high cholesterol content (20% mol), no detectable effects in the bilayer morphology or in its mechanical stability were recorded. These findings give new insights on the molecular mechanism of the amyloid/membrane interaction, highlighting the peculiar role of cholesterol.
authors.affiliation: Nanophysics, Istituto Italiano di Tecnologia , Via Morego 30, 16163 Genova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Seghezza
authors.forename: Alberto
authors.initials: A
authors.lastname: Diaspro
authors.forename: Claudio
authors.initials: C
authors.lastname: Canale
authors.forename: Silvia
authors.initials: S
authors.lastname: Dante
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D021962:Membrane Microdomains / Q000737:chemistry* / Q000648:ultrastructure; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D013109:Sphingomyelins / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010743:Phospholipids; D013109:Sphingomyelins; C075222:amyloid beta-protein (1-42); D002784:Cholesterol