title: Intrinsic and membrane-facilitated α-synuclein oligomerization revealed by label-free detection through solid-state nanopores.
abstract: 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.
authors: State Key Laboratory for Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, People's Republic of China.|Collaborative Innovation Center of Quantum Matter, 100084 Beijing, China.
authors: Rui
authors: R
authors: Hu
authors: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, Frontier Institute of Science and Technology (FIST), Xi'an Jiaotong University, Xi'an 710049, China.
authors: Jiajie
authors: J
authors: Diao
authors: State Key Laboratory for Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, People's Republic of China.|Collaborative Innovation Center of Quantum Matter, 100084 Beijing, China.
authors: Ji
authors: J
authors: Li
authors: State Key Laboratory for Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, People's Republic of China.|Collaborative Innovation Center of Quantum Matter, 100084 Beijing, China.
authors: Zhipeng
authors: Z
authors: Tang
authors: State Key Laboratory for Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, People's Republic of China.|Collaborative Innovation Center of Quantum Matter, 100084 Beijing, China.
authors: Xiaoqing
authors: X
authors: Li
authors: Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
authors: Jeremy
authors: J
authors: Leitz
authors: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, Frontier Institute of Science and Technology (FIST), Xi'an Jiaotong University, Xi'an 710049, China.
authors: Jiangang
authors: J
authors: Long
authors: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, Frontier Institute of Science and Technology (FIST), Xi'an Jiaotong University, Xi'an 710049, China.
authors: Jiankang
authors: J
authors: Liu
authors: State Key Laboratory for Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, People's Republic of China.|Collaborative Innovation Center of Quantum Matter, 100084 Beijing, China.
authors: Dapeng
authors: D
authors: Yu
authors: State Key Laboratory for Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, People's Republic of China.|Collaborative Innovation Center of Quantum Matter, 100084 Beijing, China.
authors: Qing
authors: Q
authors: Zhao
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D058608:Nanopores; D010718:Phosphatidylserines / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry; D066329:Protein Aggregates; D055503:Protein Multimerization; D021381:Protein Transport; D013499:Surface Properties; D053835:Unilamellar Liposomes / Q000737:chemistry*; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D010718:Phosphatidylserines; D011136:Polysorbates; D066329:Protein Aggregates; D053835:Unilamellar Liposomes; D051844:alpha-Synuclein; C050294:1-palmitoyl-2-oleoylglycero-3-phosphoserine; C042511:1,2-dioleoylphosphatidylserine