title: Influence of gold nanoparticle surface chemistry and diameter upon Alzheimer's disease amyloid-β protein aggregation.
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, 8 nm and 18 nm 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.
authors.affiliation: Biomedical Engineering Program, University of South Carolina, Columbia, SC 29208 USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Moore
authors.affiliation: Department of Chemical Engineering, University of South Carolina, 2C02 Swearingen Engineering Center, Columbia, SC 29208 USA.
authors.forename: Kayla M
authors.initials: KM
authors.lastname: Pate
authors.affiliation: Biomedical Engineering Program, University of South Carolina, Columbia, SC 29208 USA.
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Soto-Ortega
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801 USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Lohse
authors.affiliation: Department of Chemical Engineering, University of South Carolina, 2C02 Swearingen Engineering Center, Columbia, SC 29208 USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: van der Munnik
authors.affiliation: Department of Biological Sciences, University of South Carolina, Columbia, SC 29208 USA.
authors.forename: Mihyun
authors.initials: M
authors.lastname: Lim
authors.affiliation: Department of Biological and Physical Sciences, South Carolina State University, Orangeburg, SC 29117 USA.
authors.forename: Kaliah S
authors.initials: KS
authors.lastname: Jackson
authors.affiliation: Department of Biological and Physical Sciences, South Carolina State University, Orangeburg, SC 29117 USA.
authors.forename: Venetia D
authors.initials: VD
authors.lastname: Lyles
authors.affiliation: Department of Biological and Physical Sciences, South Carolina State University, Orangeburg, SC 29117 USA.
authors.forename: Lemeisha
authors.initials: L
authors.lastname: Jones
authors.affiliation: Department of Biological and Physical Sciences, South Carolina State University, Orangeburg, SC 29117 USA.
authors.forename: Nisha
authors.initials: N
authors.lastname: Glassgow
authors.affiliation: Department of Biological and Physical Sciences, South Carolina State University, Orangeburg, SC 29117 USA.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Napumecheno
authors.affiliation: Department of Biological and Physical Sciences, South Carolina State University, Orangeburg, SC 29117 USA.
authors.forename: Shanee
authors.initials: S
authors.lastname: Mobley
authors.affiliation: Biomedical Engineering Program, University of South Carolina, Columbia, SC 29208 USA.|Department of Chemical Engineering, University of South Carolina, 2C02 Swearingen Engineering Center, Columbia, SC 29208 USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Uline
authors.affiliation: Department of Biological and Physical Sciences, South Carolina State University, Orangeburg, SC 29117 USA.
authors.forename: Rahina
authors.initials: R
authors.lastname: Mahtab
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801 USA.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Murphy
authors.affiliation: Biomedical Engineering Program, University of South Carolina, Columbia, SC 29208 USA.|Department of Chemical Engineering, University of South Carolina, 2C02 Swearingen Engineering Center, Columbia, SC 29208 USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Moss
keywords: Aggregate morphology; Alzheimer’s disease; Amyloid-β protein; Gold nanoparticles; Inhibition; Protein aggregation