4.7 Article

Intrinsic and membrane-facilitated α-synuclein oligomerization revealed by label-free detection through solid-state nanopores

Journal

SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/srep20776

Keywords

-

Funding

  1. National 973 projects from Ministry of Science and Technology, China [2013CB932602, 2011CB707601, 2015CB856304]
  2. National Natural Science Foundation of China [NSFC51272007, 61571015, 11234001, 91433102, 11327902]
  3. Beijing Nova Program [XX2013003]

Ask authors/readers for more resources

alpha-Synuclein (alpha-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 alpha-Syn oligomerization through a label-free and single molecule approach. A tween 20 coating method is developed to inhibit non-specific adsorption between alpha-Syn and nanopore surface to ensure successful and continuous detection of alpha-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 alpha-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 alpha-Syn while do not alter the aggregation pathway.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available