Study of Wild-Type 伪-Synuclein Binding and Orientation on Gold Nanoparticles

详细信息    查看全文

• 作者：Jie An Yang ; Brittany J. Johnson ; Sway Wu ; Wendy S. Woods ; Julia M. George ; Catherine J. Murphy
• 刊名：Langmuir
• 出版年：2013
• 出版时间：April 9, 2013
• 年：2013
• 卷：29
• 期：14
• 页码：4603-4615
• 全文大小：691K
• 年卷期：v.29,no.14(April 9, 2013)
• ISSN：1520-5827

文摘

The disruption of 伪-synuclein (伪-syn) homeostasis in neurons is a potential cause of Parkinson鈥檚 disease, which is manifested pathologically by the appearance of 伪-syn aggregates, or Lewy bodies. Treatments for neurological diseases are extremely limited. To study the potential use of gold nanoparticles (Au NPs) to limit 伪-syn misfolding, the binding and orientation of 伪-syn on Au NPs were investigated. 伪-Syn was determined to interact with 20 and 90 nm Au NPs via multilayered adsorption: a strong electrostatic interaction between 伪-syn and Au NPs in the hard corona and a weaker noncovalent protein鈥損rotein interaction in the soft corona. Spectroscopic and light-scattering titrations led to the determinations of binding constants for the Au NP 伪-syn coronas: for the hard corona on 20 nm Au NPs, the equilibrium association constant was 2.9 卤 1.1 脳 10⁹ M^鈥? (for 360 卤 70 伪-syn/NP), and on 90 nm Au NPs, the hard corona association constant was 9.5 卤 0.8 脳 10¹⁰ M^鈥? (for 5300 卤 700 伪-syn/NP). The binding of the soft corona was thermodynamically unfavorable and kinetically driven and was in constant exchange with 鈥渇ree鈥?伪-syn in solution. A protease digestion method was used to deduce the 伪-syn orientation and structure on Au NPs, revealing that 伪-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 伪-syn homeostasis.