文章基本信息

标题：Intrinsic and membrane-facilitated α-synuclein oligomerization revealed by label-free detection through solid-state nanopores
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作者：Rui Hu ; Jiajie Diao ; Ji Li 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
期号：1
DOI：10.1038/srep20776
语种：English
出版社：Springer Nature
摘要：α-Synuclein (α-Syn) is an abundant cytosolic protein involved in the release of neurotransmitters in presynaptic terminal and its aberrant aggregation is found to be associated with Parkinson's disease. Recent study suggests that the oligomers formed at the initial oligomerization stage may be the root cause of cytotoxicity. While characterizing this stage is challenging due to the inherent difficulties in studying heterogeneous and transient systems by conventional biochemical technology. Here we use solid-state nanopores to study the time-dependent kinetics of α-Syn oligomerization through a label-free and single molecule approach. A tween 20 coating method is developed to inhibit non-specific adsorption between α-Syn and nanopore surface to ensure successful and continuous detection of α-Syn translocation. We identify four types of oligomers formed in oligomerization stage and find an underlying consumption mechanism that the formation of large oligomers consumes small oligomers. Furthermore, the effect of lipid membrane on oligomerization of α-Syn is also investigated and the results show that 1,2-dioleoyl-sn-glycero-3-[phospho-L-serine] (DOPS) small unilamellar vesicles (SUVs) dramatically enhances the aggregation rate of α-Syn while do not alter the aggregation pathway.