title: Nanoscale electrostatic domains in cholesterol-laden lipid membranes create a target for amyloid binding.
abstract: Amyloid fibrils are associated with multiple neurodegenerative disorders, such as Alzheimer's disease. Although biological membranes are involved in fibril plaque formation, the role of lipid membrane composition in fibril formation and toxicity is not well understood. We investigated the effect of cholesterol on the interaction of model lipid membranes with amyloid-β peptide (Aβ). With atomic force microscopy we demonstrated that binding of Aβ (1-42) to DOPC bilayer, enriched with 20% cholesterol, resulted in an intriguing formation of small nonuniform islands loaded with Aβ. We attribute this effect to the presence of nanoscale electrostatic domains induced by cholesterol in DOPC bilayers. Using frequency-modulated Kelvin probe force microscopy we were able to resolve these nanoscale electrostatic domains in DOPC monolayers. These findings directly affect our understanding of how the presence of cholesterol may induce targeted binding of amyloid deposits to biomembranes. We postulate that this nonhomogeneous electrostatic effect of cholesterol has a fundamental nature and may be present in other lipid membranes and monolayers.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Drolle
authors.forename: Ravi M
authors.initials: RM
authors.lastname: Gaikwad
authors.forename: Zoya
authors.initials: Z
authors.lastname: Leonenko
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D049329:Nanostructures / Q000737:chemistry*; D010446:Peptide Fragments / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D011485:Protein Binding; D055672:Static Electricity
chemical_list: D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010713:Phosphatidylcholines; C075222:amyloid beta-protein (1-42); D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine