Protofilaments, filaments, ribbons, and fibrils from peptidomimetic self-assembly

Implications for amyloid fibril formation and materials science

Hilal A. Lashuel, Steven R. LaBrenz, Linda Woo, Louise C. Serpell, Jeffery W. Kelly

Research output: Contribution to journalArticle

247 Citations (Scopus)

Abstract

Deciphering the mechanism(s) of β-sheet mediated self-assembly is essential for understanding amyloid fibril formation and for the fabrication of polypeptide materials. Herein, we report a simple peptidomimetic that self-assembles into polymorphic β-sheet quaternary structures including protofilaments, filaments, fibrils, and ribbons that are reminiscent of the highly ordered structures displayed by the amyloidogenic peptides Aβ, calcitonin, and amylin. The distribution of quaternary structures can be controlled by and in some cases specified by manipulating the pH, buffer composition, and the ionic strength. The ability to control β-sheet-mediated assembly takes advantage of quaternary structure dependent pK(a) perturbations. Biophysical methods including analytical ultracentrifugation studies as well as far-UV circular dichroism and FT-IR spectroscopy demonstrate that linked secondary and quaternary structural changes mediate peptidomimetic self-assembly. Electron and atomic force microscopy reveal that peptidomimetic assembly involves numerous quaternary structural intermediates that appear to self-assemble in a convergent fashion affording quaternary structures of increasing complexity. The ability to control the assembly pathway(s) and the final quaternary structure(s) afforded should prove to be particularly useful in deciphering the quaternary structural requirements for amyloid fibril formation and for the construction of noncovalent macromolecular structures.

Original languageEnglish
Pages (from-to)5262-5277
Number of pages16
JournalJournal of the American Chemical Society
Volume122
Issue number22
DOIs
Publication statusPublished - 7 Jun 2000
Externally publishedYes

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Peptidomimetics
Materials science
Amyloid
Self assembly
Islet Amyloid Polypeptide
Atomic Force Microscopy
Polypeptides
Ultracentrifugation
Calcitonin
Dichroism
Circular Dichroism
Ionic strength
Osmolar Concentration
Peptides
Infrared spectroscopy
Atomic force microscopy
Spectrum Analysis
Buffers
Electrons
Fabrication

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Protofilaments, filaments, ribbons, and fibrils from peptidomimetic self-assembly : Implications for amyloid fibril formation and materials science. / Lashuel, Hilal A.; LaBrenz, Steven R.; Woo, Linda; Serpell, Louise C.; Kelly, Jeffery W.

In: Journal of the American Chemical Society, Vol. 122, No. 22, 07.06.2000, p. 5262-5277.

Research output: Contribution to journalArticle

Lashuel, Hilal A. ; LaBrenz, Steven R. ; Woo, Linda ; Serpell, Louise C. ; Kelly, Jeffery W. / Protofilaments, filaments, ribbons, and fibrils from peptidomimetic self-assembly : Implications for amyloid fibril formation and materials science. In: Journal of the American Chemical Society. 2000 ; Vol. 122, No. 22. pp. 5262-5277.
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