Hexafluoroisopropanol induces self-assembly of β-amyloid peptides into highly ordered nanostructures

Authors

  • Sanjai Kumar Pachahara,

    1. Council of Scientific and Industrial Research, Centre for Cellular and Molecular Biology, Hyderabad, India
    Search for more papers by this author
    • §

      These authors have contributed equally to this work.

  • Nitin Chaudhary,

    1. Council of Scientific and Industrial Research, Centre for Cellular and Molecular Biology, Hyderabad, India
    Search for more papers by this author
    • Current address: Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, 781 039, Assam, India

    • §

      These authors have contributed equally to this work.

  • Chilukuri Subbalakshmi,

    1. Council of Scientific and Industrial Research, Centre for Cellular and Molecular Biology, Hyderabad, India
    Search for more papers by this author
  • Ramakrishnan Nagaraj

    Corresponding author
    • Council of Scientific and Industrial Research, Centre for Cellular and Molecular Biology, Hyderabad, India
    Search for more papers by this author

Ramakrishnan Nagaraj, Council of Scientific and Industrial Research, Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India. E-mail: nraj@ccmb.res.in

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. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

Ancillary