Single molecule characterization of the interactions between amyloid-β peptides and the membranes of hippocampal cells.
Single molecule characterization of the interactions between amyloid-β peptides and the membranes of hippocampal cells.
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DOI：
10.1021/ja3103567
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发表时间：
2013-01-30
影响因子：
15
通讯作者：
Klenerman, David
中科院分区：
文献类型：
--
作者：
Narayan, Priyanka;Ganzinger, Kristina A.;McColl, James;Weimann, Laura;Meehan, Sarah;Qamar, Seema;Carver, John A.;Wilson, Mark R.;George-Hyslop, Peter St.;Dobson, Christopher M.;Klenerman, David
40和42残基淀粉样多肽(Aβ40和Aβ42)的寡聚体与阿尔茨海默病相关的神经元损伤和认知功能受损有关。然而，关于这些错误折叠的物种对细胞产生如此有害影响的具体机制，人们知之甚少。在这项工作中，我们使用单分子成像技术来研究Aβ单体和低聚物与活细胞膜之间的初始相互作用。这种高度灵敏的方法使单个Aβ物种在细胞表面的可视化和其寡聚状态的表征成为可能，所有这些都是在生物相关的纳摩尔浓度下进行的。结果表明，相对于单体，低聚物优先与细胞膜相互作用，低聚物被固定在细胞表面。此外，我们观察到Aβ物种与细胞膜的相互作用被不依赖于ATP的分子伴侣的存在所抑制。这项研究展示了这种方法在生理相关浓度下表征蛋白质聚集体与活神经元细胞膜之间相互作用的能力，并为定量研究细胞对潜在致病低聚物的反应打开了大门。
Oligomers of the 40 and 42 residue amyloid-β peptides (Aβ40 and Aβ42) have been implicated in the neuronal damage and impaired cognitive function associated with Alzheimer’s disease. However, little is known about the specific mechanisms by which these misfolded species induce such detrimental effects on cells. In this work, we use single-molecule imaging techniques to examine the initial interactions between Aβ monomers and oligomers and the membranes of live cells. This highly sensitive method enables the visualization of individual Aβ species on the cell surface and characterization of their oligomerization state, all at biologically relevant, nanomolar concentrations. The results indicate that oligomers preferentially interact with cell membranes, relative to monomers and that the oligomers become immobilized on the cell surface. Additionally, we observe that the interaction of Aβ species with the cell membrane is inhibited by the presence of ATP-independent molecular chaperones. This study demonstrates the power of this methodology for characterizing the interactions between protein aggregates and the membranes of live neuronal cells at physiologically relevant concentrations and opens the door to quantitative studies of the cellular responses to potentially pathogenic oligomers.
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影响因子：
4
作者：
Bolognesi, Benedetta;Kumita, Janet R.;Yerbury, Justin J.
通讯作者：
Yerbury, Justin J.
影响因子：
--
作者：
Mehta, PD;Pirttilä, T;Wisniewski, HM
通讯作者：
Wisniewski, HM
DOI：
10.1073/pnas.1117799109
发表时间：
2012-07-31
影响因子：
11.1
作者：
Mannini, Benedetta;Cascella, Roberta;Chiti, Fabrizio
通讯作者：
Chiti, Fabrizio
影响因子：
3.4
作者：
Kawahara, M;Arispe, N;Rojas, E
通讯作者：
Rojas, E
影响因子：
3.7
作者：
Johnson RD;Schauerte JA;Wisser KC;Gafni A;Steel DG
通讯作者：
Steel DG