Nanoparticle‐Induced Folding and Fibril Formation of Coiled‐Coil‐Based Model Peptides

Abstract

Nanomedicine is a rapidly growing field that has the potential to deliver treatments for many illnesses. However, relatively little is known about the biological risks of nanoparticles. Some studies have shown that nanoparticles can have an impact on the aggregation properties of proteins, including fibril formation. Moreover, these studies also show that the capacity of nanoscale objects to induce or prevent misfolding of the proteins strongly depends on the primary structure of the protein. Herein, light is shed on the role of the peptide primary structure in directing nanoparticle-induced misfolding by means of two model peptides. The design of these peptides is based on the alpha-helical coiled-coil folding motif, but also includes features that enable them to respond to pH changes, thus allowing pH-dependent beta-sheet formation. Previous studies showed that the two peptides differ in the pH range required for beta-sheet folding. Time-dependent circular dichroism spectroscopy and transmission electron microscopy are used to characterize peptide folding and aggregate morphology in the presence of negatively charged gold nanoparticles (AuNPs). Both peptides are found to undergo nanoparticle-induced fibril formation. The determination of binding parameters by isothermal titration calorimetry further reveals that the different propensities of both peptides to form amyloid-like structures in the presence of AuNPs is primarily due to the binding stoichiometry to the AuNPs. Modification of one of the peptide sequences shows that AuNP-induced beta-sheet formation is related to the structural propensity of the primary structure and is not a generic feature of peptide sequences with a sufficiently high binding stoichiometry to the nanoparticles.

Interaction of nanoparticles with proteins: relation to bio-reactivity of the nanoparticle

“…NPs can also induce conformational changes in proteins that can lead to fibril formation [37,38]. Linse et al showed that a range of NPs (copolymer, ceria, carbon nanotubes, quantum dots) were capable of inducing fibrillation of β2-microglobulindue to increased protein localization on the NP surface, which led to oligomer formation [39].…”

Impact of multivalent charge presentation on peptide–nanoparticle aggregation

“…It is known that gold nanoparticles may affect the secondary structure of a peptide or protein [33]. To investigate the effect of Au/MUA nanoparticles on the secondary structure of the peptides included in this study, CD spectroscopy was applied with a peptide concentration of 15 µM and 0.05 µM Au/MUA nanoparticle concentration.…”

“…Recently we published the use of coiled-coil model peptide VW05 for the reversible assembly of mercaptoundecanoic acid functionalized gold nanoparticles using electrostatic interactions [32–33]. We showed that the interaction can be repeatedly switched by adjusting the pH value.…”

Photonics and plasmonics go viral: self-assembly of hierarchical metamaterials

“…Synthetic approaches have also been devised and include the chemical programming of hierarchical structures, such as seen in the synthesis of branched dendrimer systems (Bergamini et al 2011; Furuta et al 2003; Miura et al 2011; Mynar et al 2006; Nantalaksakul et al 2006; Serin et al 2002). Other developments include the use of synthetic block copolymers (Zhao et al 2009) or application of orthogonal pairs of coiled-coil peptides (Stevens et al 2004; Wagner et al 2010) to induce self-assembly of nanoparticles. It is clear that self-assembly holds great potential for the manufacturing of mesoscale materials through simple solution-based bottom-up synthesis.…”