Can small hydrophobic gold nanoparticles inhibit β2-microglobulin fibrillation?
- 22 April 2014
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Nanoscale
- Vol. 6 (14), 7903-7911
- https://doi.org/10.1039/c4nr01514b
Abstract
Inorganic nanoparticles stabilized by a shell of organic ligands can enhance or suppress the natural propensity of proteins to form fibrils. Functionalization facilitates targeted delivery of the nanoparticles to various cell types, bioimaging, drug delivery and other therapeutic and diagnostic applications. In this study, we provide a computational model of the effect of a prototypical thiol-protected gold nanoparticle, Au25L18 − (L = S(CH2)2Ph) on the β2-microglobulin natural fibrillation propensity. To reveal the molecular basis of the protein–nanoparticle association process, we performed various simulations at multiple levels (Classical Molecular Dynamics and Brownian Dynamics) that cover multiple length- and timescales. The results provide a model of the ensemble of structures constituting the protein–gold nanoparticle complexes, and insights into the driving forces for the binding of β2-microglobulin to hydrophobic small size gold nanoparticles. We have found that the small nanoparticles can bind the protein to form persistent complexes. This binding of nanoparticles is able to block the active sites of domains from binding to another protein, thus leading to potential inhibition of the fibrillation activity. A comparison with the binding patches identified for the interaction of the protein with a known inhibitor of fibrillation, supports our conclusion.Keywords
This publication has 49 references indexed in Scilit:
- Nanoparticle safety in doubtNature, 2009
- Influence of fluorinated and hydrogenated nanoparticles on the structure and fibrillogenesis of amyloid beta-peptideBiophysical Chemistry, 2008
- Application of Nanotechnology in Cancer Therapy and ImagingCA: A Cancer Journal for Clinicians, 2008
- Nucleation of protein fibrillation by nanoparticlesProceedings of the National Academy of Sciences, 2007
- PEGylated phospholipid nanomicelles interact with β-amyloid(1–42) and mitigate its β-sheet formation, aggregation and neurotoxicity in vitroPeptides, 2006
- Protein Misfolding, Functional Amyloid, and Human DiseaseAnnual Review of Biochemistry, 2006
- Oligonucleotide-Modified Gold Nanoparticles for Intracellular Gene RegulationScience, 2006
- Nanoparticle PCR: Nanogold‐Assisted PCR with Enhanced SpecificityAngewandte Chemie-International Edition, 2005
- Quantum Dots for Live Cells, in Vivo Imaging, and DiagnosticsScience, 2005
- Fullerene inhibits β-amyloid peptide aggregationBiochemical and Biophysical Research Communications, 2003