Multivalent macromolecules redirect nucleation-dependent fibrillar assembly into discrete nanostructures

Yang Song, Pin Nan Cheng, Lijuan Zhu, Edwin G. Moore, Jeffrey S. Moore

Research output: Contribution to journalArticlepeer-review

Abstract

Manipulating the size and shape of noncovalent multivalent assemblies is an ongoing challenge in the field of supramolecular polymers. Following a mechanistic approach, we reasoned that nucleation-elongation kinetics presents unique opportunities for controlled growth since the final outcome is likely to depend on the structure and dynamics of critical-nucleus formation. Taking fibrillar assembly of amyloid β (Aβ) peptide as the model system of nucleation-dependent supramolecular polymerization, here we report multivalent polymer-peptide conjugates (mPPCs) that redirect fibrillar assembly of Aβ to form discrete nanostructures. The mPPCs were rationally designed to target Aβ intermediates formed prior to critical nucleation. Atomic force microscopy and transmission electron microscopy studies show that in the presence of mPPCs, Aβ self-assembles into zero-dimensional discrete nanostructures with lateral dimensions approximately in 5-35 nm, while Aβ alone self-assembles into one-dimensional fibrils in micrometer. Thioflavin T kinetics fluorescence assays demonstrate that mPPCs suppress Aβ fibrillogenesis. The mPPCs may thus represent a prototypical molecular design of multivalent macromolecules able to control the final shape of supramolecular polymers assembled via a nucleation-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)5233-5236
Number of pages4
JournalJournal of the American Chemical Society
Volume136
Issue number14
DOIs
StatePublished - Apr 9 2014

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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