Real-Time Characterization of Cell Membrane Disruption by α-Synuclein Oligomers in Live SH-SY5Y Neuroblastoma Cells
Real-Time Characterization of Cell Membrane Disruption by α-Synuclein Oligomers in Live SH-SY5Y Neuroblastoma Cells
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DOI：
10.1021/acschemneuro.0c00309
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发表时间：
2020-09-02
影响因子：
5
通讯作者：
Wang, Yixian
中科院分区：
文献类型：
--
作者：
Parres-Gold, Jacob;Chieng, Andy;Wang, Yixian
天然未折叠蛋白α-突触核蛋白（α-Syn）的聚集与帕金森病相关的神经元死亡广泛相关。突变和蛋白质过度积累可促进α-Syn聚集成寡聚体和原纤维。最近的研究表明，α-Syn寡聚体可以透化神经元膜，促进钙内流和细胞死亡。然而，这种透化的机制仍然是不确定的，尚未在活细胞中进行表征。这项工作使用扫描离子电导显微镜（SICM）的图像，在真实的时间，而不使用化学探针，活的SH-SY 5 Y神经母细胞瘤细胞暴露于α-Syn寡聚体后的形貌。观察到大量的形态学变化，在较低的α-Syn浓度（1.00 μ M）下观察到微米级的山丘和低谷，在较高的α-Syn浓度（6.0 μ M）下观察到大的瞬时孔。这些发现表明，α-Syn寡聚体可以通过使脂质双层不稳定和打开瞬时孔来透化神经元膜。
Aggregation of the natively unfolded protein alpha-synuclein (alpha-Syn) has been widely correlated to the neuronal death associated with Parkinson's disease. Mutations and protein overaccumulation can promote the aggregation of alpha-Syn into oligomers and fibrils. Recent work has suggested that alpha-Syn oligomers can permeabilize the neuronal membrane, promoting calcium influx and cell death. However, the mechanism of this permeabilization is still uncertain and has yet to be characterized in live cells. This work uses scanning ion conductance microscopy (SICM) to image, in real time and without using chemical probes, the topographies of live SH-SY5Y neuroblastoma cells after exposure to alpha-Syn oligomers. Substantial morphological changes were observed, with micrometer-scale hills and troughs observed at lower alpha-Syn concentrations (1.00 mu M) and large, transient pores observed at higher alpha-Syn concentrations (6.0 mu M). These findings suggest that alpha-Syn oligomers may permeabilize the neuronal membrane by destabilizing the lipid bilayer and opening transient pores.