title: Interaction of the amyloid β peptide with sodium dodecyl sulfate as a membrane-mimicking detergent.
abstract: The amyloid β (A β) peptide is important in the context of Alzheimer's disease, since it is one of the major components of the fibrils that constitute amyloid plaques. Agents that can influence fibril formation are important, and of those, membrane mimics are particularly relevant, because the hydrophobic part of A β suggests a possible membrane activity of the peptide. We employed spin-label EPR to investigate the aggregation process of A β1-40 in the presence of the sodium dodecyl sulfate (SDS) detergent as a membrane-mimicking agent. In this work, the effect of SDS on A β is studied using two positions of spin label, the N-terminus and position 26. By comparing the two label positions, the effect of local mobility of the spin label is eliminated, revealing A β aggregation in the SDS concentration regime below the critical micelle concentration (CMC). We demonstrate that, at low SDS concentrations, the N-terminus of A β participates in the solubilization, most likely by being located at the particle-water interface. At higher SDS concentrations, an SDS-solubilized state that is a precursor to the one A β/micelle state above the CMC of SDS prevails. We propose that A β is membrane active and that aggregates include SDS. This study reveals the unique potential of EPR in studying A β aggregation in the presence of detergent.
authors.affiliation: Department of Physics, Huygens-Kamerlingh Onnes Laboratory, P.O. Box 9504, 2300, RA, Leiden, The Netherlands.
authors.forename: Maryam Hashemi
authors.initials: MH
authors.lastname: Shabestari
authors.affiliation: Leiden Institute of Chemistry, Leiden University, NL-2300, RA, Leiden, The Netherlands.
authors.forename: Nico J
authors.initials: NJ
authors.lastname: Meeuwenoord
authors.affiliation: Leiden Institute of Chemistry, Leiden University, NL-2300, RA, Leiden, The Netherlands.
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Filippov
authors.affiliation: Department of Physics, Huygens-Kamerlingh Onnes Laboratory, P.O. Box 9504, 2300, RA, Leiden, The Netherlands. huber@physics.leidenuniv.nl.
authors.forename: Martina
authors.initials: M
authors.lastname: Huber
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D003902:Detergents / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008567:Membranes, Artificial; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012399:Rotation; D012967:Sodium Dodecyl Sulfate / Q000378:metabolism* / Q000494:pharmacology; D013113:Spin Labels
chemical_list: D016229:Amyloid beta-Peptides; D003902:Detergents; D008567:Membranes, Artificial; D010446:Peptide Fragments; D013113:Spin Labels; C078592:amyloid beta-protein (1-40); D012967:Sodium Dodecyl Sulfate
keywords: Alzheimer’s disease; Amyloid membrane interaction; Amyloid-beta 1–40; Amyloid-beta SDS interaction; Electron paramagnetic resonance (EPR)