Rapid detection of Aβ aggregation and inhibition by dual functions of gold nanoplasmic particles: Catalytic activator and optical reporter

Inhee Choi, Luke P. Lee

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

One of the primary pathological hallmarks of Alzheimer's diseases (AD) is amyloid-β (Aβ) aggregation and its extracellular accumulation. However, current in vitro Aβ aggregation assays require time-consuming and labor-intensive steps, which delay the process of drug discovery and understanding the mechanism of Aβ induced neurotoxicity. Here, we propose a rapid detection method for studying Aβ aggregation and inhibition under an optimized acidic perturbation condition by dual functions of gold nanoplasmonic particles (GNPs): (1) catalytic activator and (2) optical reporter. Because of roles of GNPs as effective nucleation sites for fast-catalyzing Aβ aggregation and colorimetric optical reporters for tracking Aβ aggregation, we accomplished the fast aggregation assay in less than 1 min by the naked eyes. Our detection method is based on spontaneous clustering of unconjugated (unmodified) GNPs along with the aggregated Aβ network under an aggregation-promoting condition. As a proof-of-concept demonstration, we employed the acidic perturbation permitting rapid cooperative assemblies of GNPs and Aβ peptides via their surface charge modulation. Under the optimized acidic perturbation condition around pH 2 to 3, we characterized the concentration-dependent colorimetric responses for aggregation at physiologically relevant Aβ concentration levels (from 100 μM to 10 nM). We also demonstrated the GNP/acidic condition-based rapid inhibition assay of Aβ aggregation by using well-known binding reagents such as antibody and serum albumin. The proposed methodology can be a powerful alternative method for screening drugs for AD as well as studying molecular biophysics of protein aggregations, and further extended to explore other protein conformational diseases such as neurodegenerative disease.

Original languageEnglish
Pages (from-to)6268-6277
Number of pages10
JournalACS Nano
Volume7
Issue number7
DOIs
StatePublished - 23 Jul 2013

Keywords

  • Alzheimer's disease
  • amyloid-β
  • colorimetric
  • drug screening
  • light scattering
  • nanoparticle
  • nanoplasmonics
  • nucleation

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