Study of wild-type α-synuclein binding and orientation on gold nanoparticles

Jie An Yang, Brittany J. Johnson, Sway Wu, Wendy S. Woods, Julia M. George, Catherine J. Murphy

Research output: Contribution to journalArticle

Abstract

The disruption of α-synuclein (α-syn) homeostasis in neurons is a potential cause of Parkinson's disease, which is manifested pathologically by the appearance of α-syn aggregates, or Lewy bodies. Treatments for neurological diseases are extremely limited. To study the potential use of gold nanoparticles (Au NPs) to limit α-syn misfolding, the binding and orientation of α-syn on Au NPs were investigated. α-Syn was determined to interact with 20 and 90 nm Au NPs via multilayered adsorption: a strong electrostatic interaction between α-syn and Au NPs in the hard corona and a weaker noncovalent protein-protein interaction in the soft corona. Spectroscopic and light-scattering titrations led to the determinations of binding constants for the Au NP α-syn coronas: for the hard corona on 20 nm Au NPs, the equilibrium association constant was 2.9 ± 1.1 × 109 M-1 (for 360 ± 70 α-syn/NP), and on 90 nm Au NPs, the hard corona association constant was 9.5 ± 0.8 × 1010 M-1 (for 5300 ± 700 α-syn/NP). The binding of the soft corona was thermodynamically unfavorable and kinetically driven and was in constant exchange with "free" α-syn in solution. A protease digestion method was used to deduce the α-syn orientation and structure on Au NPs, revealing that α-syn absorbs onto negatively charged Au NPs via its N-terminus while apparently retaining its natively unstructured conformation. These results suggest that Au NPs could be used to sequester and regulate α-syn homeostasis.

Original languageEnglish (US)
Pages (from-to)4603-4615
Number of pages13
JournalLangmuir
Volume29
Issue number14
DOIs
StatePublished - Apr 9 2013

ASJC Scopus subject areas

  • Materials Science(all)
  • Condensed Matter Physics
  • Surfaces and Interfaces
  • Spectroscopy
  • Electrochemistry

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    Yang, J. A., Johnson, B. J., Wu, S., Woods, W. S., George, J. M., & Murphy, C. J. (2013). Study of wild-type α-synuclein binding and orientation on gold nanoparticles. Langmuir, 29(14), 4603-4615. https://doi.org/10.1021/la400266u