Influence of Nanoparticle Size and Shape on Oligomer Formation of an Amyloidogenic Peptide

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-a...

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Veröffentlicht in:The journal of physical chemistry letters 2011-05, Vol.2 (10), p.1171-1177
Hauptverfasser: O’Brien, Edward P, Straub, John. E, Brooks, Bernard R, Thirumalai, D
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Sprache:eng
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Zusammenfassung: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.
ISSN:1948-7185
1948-7185
DOI:10.1021/jz200330k