title: Hexafluoroisopropanol induces self-assembly of β-amyloid peptides into highly ordered nanostructures.
abstract: Deposition of insoluble fibrillar aggregates of β-amyloid (Aβ) peptides in the brain is a hallmark of Alzheimer's disease. Apart from forming fibrils, these peptides also exist as soluble aggregates. Fibrillar and a variety of nonfibrillar aggregates of Aβ have also been obtained in vitro. Hexafluoroisopropanol (HFIP) has been widely used to dissolve Aβ and other amyloidogenic peptides. In this study, we show that the dissolution of Aβ40, 42, and 43 in HFIP followed by drying results in highly ordered aggregates. Although α-helical conformation is observed, it is not stable for prolonged periods. Drying after prolonged incubation of Aβ40, 42, and 43 peptides in HFIP leads to structural transition from α-helical to β-conformation. The peptides form short fibrous aggregates that further assemble giving rise to highly ordered ring-like structures. Aβ16-22, a highly amyloidogenic peptide stretch from Aβ, also formed very similar rings when dissolved in HFIP and dried. HFIP could not induce α-helical conformation in Aβ16-22, and rings were obtained from freshly dissolved peptide. The rings formed by Aβ40, 42, 43, and Aβ16-22 are composed of the peptides in β-conformation and cause enhancement in thioflavin T fluorescence, suggesting that the molecular architecture of these structures is amyloid-like. Our results clearly indicate that dissolution of Aβ40, 42 and 43 and the amyloidogenic fragment Aβ16-22 in HFIP results in the formation of annular amyloid-like structures.
authors.affiliation: Council of Scientific and Industrial Research, Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.
authors.forename: Sanjai Kumar
authors.initials: SK
authors.lastname: Pachahara
authors.forename: Nitin
authors.initials: N
authors.lastname: Chaudhary
authors.forename: Chilukuri
authors.initials: C
authors.lastname: Subbalakshmi
authors.forename: Ramakrishnan
authors.initials: R
authors.lastname: Nagaraj
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D052160:Benzothiazoles; D002942:Circular Dichroism; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D010446:Peptide Fragments / Q000737:chemistry*; D020005:Propanols / Q000737:chemistry*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013844:Thiazoles / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D020005:Propanols; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C098994:amyloid beta-protein (1-43); C009462:thioflavin T; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated