Study of wild-type α-synuclein binding and orientation on gold nanoparticles
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 nano...
| Veröffentlicht in: | Langmuir : the ACS journal of surfaces and colloids. - 1992. - 29(2013), 14 vom: 09. Apr., Seite 4603-15 |
|---|---|
| 1. Verfasser: | |
| Weitere Verfasser: | , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2013
|
| Zugriff auf das übergeordnete Werk: | Langmuir : the ACS journal of surfaces and colloids |
| Schlagworte: | Journal Article Research Support, U.S. Gov't, Non-P.H.S. alpha-Synuclein Gold 7440-57-5 Trypsin EC 3.4.21.4 |
| Zusammenfassung: | 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 × 10(9) M(-1) (for 360 ± 70 α-syn/NP), and on 90 nm Au NPs, the hard corona association constant was 9.5 ± 0.8 × 10(10) 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 |
|---|---|
| Beschreibung: | Date Completed 20.09.2013 Date Revised 09.04.2022 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1520-5827 |
| DOI: | 10.1021/la400266u |