title: Single molecule characterization of the interactions between amyloid-β peptides and the membranes of hippocampal cells.
abstract: 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.
authors: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, United Kingdom CB2 1EW.
authors: Priyanka
authors: P
authors: Narayan
authors: Kristina A
authors: KA
authors: Ganzinger
authors: James
authors: J
authors: McColl
authors: Laura
authors: L
authors: Weimann
authors: Sarah
authors: S
authors: Meehan
authors: Seema
authors: S
authors: Qamar
authors: John A
authors: JA
authors: Carver
authors: Mark R
authors: MR
authors: Wilson
authors: Peter
authors: P
authors: St George-Hyslop
authors: Christopher M
authors: CM
authors: Dobson
authors: David
authors: D
authors: Klenerman
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry*; D004058:Diffusion; D006624:Hippocampus / Q000737:chemistry* / Q000166:cytology; D006801:Humans; D010316:Particle Size; D011994:Recombinant Proteins / Q000737:chemistry; D013499:Surface Properties
chemical_list: D016229:Amyloid beta-Peptides; D011994:Recombinant Proteins