Single Molecule Characterization of the Interactions between Amyloid-尾 Peptides and the Membranes of Hippocampal Cells

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• 作者：Priyanka Narayan ; Kristina A. Ganzinger ; James McColl ; Laura Weimann ; Sarah Meehan ; Seema Qamar ; John A. Carver ; Mark R. Wilson ; Peter St. George-Hyslop ; Christopher M. Dobson ; David Klenerman
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：January 30, 2013
• 年：2013
• 卷：135
• 期：4
• 页码：1491-1498
• 全文大小：464K
• 年卷期：v.135,no.4(January 30, 2013)
• ISSN：1520-5126

文摘

Oligomers of the 40 and 42 residue amyloid-尾 peptides (A尾40 and A尾42) have been implicated in the neuronal damage and impaired cognitive function associated with Alzheimer鈥檚 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 A尾 monomers and oligomers and the membranes of live cells. This highly sensitive method enables the visualization of individual A尾 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 A尾 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.