title: Secondary structure and interfacial aggregation of amyloid-beta(1-40) on sodium dodecyl sulfate micelles.
abstract: Alzheimer's disease (AD) is characterized by the presence of large numbers of fibrillar amyloid deposits in the form of senile plaques in the brain. The fibrils in senile plaques are composed of 40- and 42-residue amyloid-beta (Abeta) peptides. Several lines of evidence indicate that fibrillar Abeta and especially soluble Abeta aggregates are important in the pathogenesis of AD, and many laboratories have investigated soluble Abeta aggregates generated from monomeric Abeta in vitro. Of these in vitro aggregates, the best characterized are called protofibrils. They are composed of globules and short rods, show primarily beta-structure by circular dichroism (CD), enhance the fluorescence of bound thioflavin T, and readily seed the growth of long fibrils. However, one difficulty in correlating soluble Abeta aggregates formed in vitro with those in vivo is the high probability that cellular interfaces affect the aggregation rates and even the aggregate structures. Reports that focus on the features of interfaces that are important in Abeta aggregation have found that amphiphilic interactions and micellar-like Abeta structures may play a role. We previously described the formation of Abeta(1-40) aggregates at polar-nonpolar interfaces, including those generated at microdroplets formed in dilute hexafluoro-2-propanol (HFIP). Here we compared the Abeta(1-40) aggregates produced on sodium dodecyl sulfate (SDS) micelles, which may be a better model of biological membranes with phospholipids that have anionic headgroups. At both HFIP and SDS interfaces, changes in peptide secondary structure were observed by CD immediately when Abeta(1-40) was introduced. With HFIP, the change involved an increase in predominant beta-structure content and in fluorescence with thioflavin T, while with SDS, a partial alpha-helical conformation was adopted that gave no fluorescence. However, in both systems, initial amorphous clustered aggregates progressed to soluble fibers rich in beta-structure over a roughly 2 day period. Fiber formation was much faster than in the absence of an interface, presumably because of the close intermolecular proximity of peptides at the interfaces. While these fibers resembled protofibrils, they failed to seed the aggregation of Abeta(1-40) monomers effectively.
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors.forename: Vijayaraghavan
authors.initials: V
authors.lastname: Rangachari
authors.forename: Dana Kim
authors.initials: DK
authors.lastname: Reed
authors.forename: Brenda D
authors.initials: BD
authors.lastname: Moore
authors.forename: Terrone L
authors.initials: TL
authors.lastname: Rosenberry
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D002942:Circular Dichroism; D006801:Humans; D008823:Micelles; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000648:ultrastructure; D020005:Propanols / Q000737:chemistry; D017433:Protein Structure, Secondary; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated
chemical_list: D016229:Amyloid beta-Peptides; D008823:Micelles; D010446:Peptide Fragments; D020005:Propanols; D012967:Sodium Dodecyl Sulfate; C078592:amyloid beta-protein (1-40); C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated