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

TL;DR

This study uses molecular simulations to explore how nanoparticle size and shape affect amyloid peptide oligomer formation, revealing that smaller and differently shaped nanoparticles influence early aggregation stages.

Contribution

It provides new insights into how nanoparticle size and shape modulate amyloid peptide aggregation, highlighting the importance of depletion effects and particle geometry.

Findings

Smaller nanoparticles destabilize dimers but stabilize trimers and tetramers.

Larger nanoparticles have reduced effects on aggregation.

Shape influences stability, with spherocylindrical particles destabilizing dimers more than spherical ones.

Abstract

Understanding the influence of macromolecular crowding and nanoparticles on the formation of in-register $\beta$-sheets, the primary structural component of amyloid fibrils, is a first step towards describing \emph{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 $\beta$-sheets formed by dimers while stabilizing $\beta$-sheets comprised of trimers and tetramers. As the radius of the nanoparticle increases crowding effects decrease, implying 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 $\beta$-sheet dimer to a greater extent than spherical crowders, which underscores the influence of nanoparticle shape on protein aggregation.