Influence of nanoparticle size and shape on oligomer formation of an amyloidogenic peptide

Edward P. Obrien, John E. Straub, Bernard R. Brooks, D. Thirumalai

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Understanding the influence of macromolecular crowding and nanoparticles on the formation of in-register β-sheets, the primary structural component of amyloid fibrils, is a first step toward describing in vivo protein aggregation and interactions between synthetic materials and proteins. Using all-atom molecular simulations in implicit solvent, we illustrate the effects of nanoparticle size, shape, and volume fraction on oligomer formation of an amyloidogenic peptide from the transthyretin protein. Surprisingly, we find that inert spherical crowding particles destabilize in-register β-sheets formed by dimers while stabilizing β-sheets comprised of trimers and tetramers. As the radius of the nanoparticle increases, crowding effects decrease, implying that smaller crowding particles have the largest influence on the earliest amyloid species. We explain these results using a theory based on the depletion effect. Finally, we show that spherocylindrical crowders destabilize the ordered β-sheet dimer to a greater extent than spherical crowders, which underscores the influence of nanoparticle shape on protein aggregation.

Original languageEnglish (US)
Pages (from-to)1171-1177
Number of pages7
JournalJournal of Physical Chemistry Letters
Issue number10
StatePublished - May 19 2011

All Science Journal Classification (ASJC) codes

  • General Materials Science
  • Physical and Theoretical Chemistry


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