Influence of gold nanoparticle surface chemistry and diameter upon Alzheimer's disease amyloid-β protein aggregation

Kelly A. Moore, Kayla M. Pate, Deborah D. Soto-Ortega, Samuel Lohse, Nicholas van der Munnik, Mihyun Lim, Kaliah S. Jackson, Venetia D. Lyles, Lemeisha Jones, Nisha Glassgow, Vanessa M. Napumecheno, Shanee Mobley, Mark J. Uline, Rahina Mahtab, Catherine J. Murphy, Melissa A. Moss

Research output: Contribution to journalArticle

Abstract

Background: Deposits of aggregated amyloid-β protein (Aβ) are a pathological hallmark of Alzheimer's disease (AD). Thus, one therapeutic strategy is to eliminate these deposits by halting Aβ aggregation. While a variety of possible aggregation inhibitors have been explored, only nanoparticles (NPs) exhibit promise at low substoichiometric ratios. With tunable size, shape, and surface properties, NPs present an ideal platform for rationally designed Aβ aggregation inhibitors. In this study, we characterized the inhibitory capabilities of gold nanospheres exhibiting different surface coatings and diameters. Results: Both NP diameter and surface chemistry were found to modulate the extent of aggregation, while NP electric charge influenced aggregate morphology. Notably, 8nm and 18nm poly(acrylic acid)-coated NPs abrogated Aβ aggregation at a substoichiometric ratio of 1:2,000,000. Theoretical calculations suggest that this low stoichiometry could arise from altered solution conditions near the NP surface. Specifically, local solution pH and charge density are congruent with conditions that influence aggregation. Conclusions: These findings demonstrate the potential of surface-coated gold nanospheres to serve as tunable therapeutic agents for the inhibition of Aβ aggregation. Insights gained into the physiochemical properties of effective NP inhibitors will inform future rational design of effective NP-based therapeutics for AD.

Original languageEnglish (US)
Article number5
JournalJournal of Biological Engineering
Volume11
Issue number1
DOIs
StatePublished - Feb 6 2017

Keywords

  • Aggregate morphology
  • Alzheimer's disease
  • Amyloid-β protein
  • Gold nanoparticles
  • Inhibition
  • Protein aggregation

ASJC Scopus subject areas

  • Environmental Engineering
  • Biomedical Engineering
  • Molecular Biology
  • Cell Biology

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    Moore, K. A., Pate, K. M., Soto-Ortega, D. D., Lohse, S., van der Munnik, N., Lim, M., Jackson, K. S., Lyles, V. D., Jones, L., Glassgow, N., Napumecheno, V. M., Mobley, S., Uline, M. J., Mahtab, R., Murphy, C. J., & Moss, M. A. (2017). Influence of gold nanoparticle surface chemistry and diameter upon Alzheimer's disease amyloid-β protein aggregation. Journal of Biological Engineering, 11(1), [5]. https://doi.org/10.1186/s13036-017-0047-6