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Single molecule characterization of the interactions between amyloid-β peptides and the membranes of hippocampal cells

Journal Article


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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


  •   Narayan, Priyanka (external author)
  •   Ganzinger, K A. (external author)
  •   Mccoll, James (external author)
  •   Weimann, Laura (external author)
  •   Meehan, Sarah (external author)
  •   Qamar, Seema (external author)
  •   Carver, John A. (external author)
  •   Mark R Wilson
  •   George-Hyslop, Peter St. (external author)
  •   Dobson, Christopher M. (external author)
  •   Klenerman, David (external author)

Publication Date


  • 2013

Citation


  • Narayan, P., Ganzinger, K. A., Mccoll, J., Weimann, L., Meehan, S., Qamar, S., Carver, J. A., Wilson, M. R., George-Hyslop, P. St., Dobson, C. M. & Klenerman, D. (2013). Single molecule characterization of the interactions between amyloid-β peptides and the membranes of hippocampal cells. Journal of the American Chemical Society, 135 (4), 1491-1498.

Scopus Eid


  • 2-s2.0-84873809834

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1321&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/309

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 1491

End Page


  • 1498

Volume


  • 135

Issue


  • 4

Place Of Publication


  • United States

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


  •   Narayan, Priyanka (external author)
  •   Ganzinger, K A. (external author)
  •   Mccoll, James (external author)
  •   Weimann, Laura (external author)
  •   Meehan, Sarah (external author)
  •   Qamar, Seema (external author)
  •   Carver, John A. (external author)
  •   Mark R Wilson
  •   George-Hyslop, Peter St. (external author)
  •   Dobson, Christopher M. (external author)
  •   Klenerman, David (external author)

Publication Date


  • 2013

Citation


  • Narayan, P., Ganzinger, K. A., Mccoll, J., Weimann, L., Meehan, S., Qamar, S., Carver, J. A., Wilson, M. R., George-Hyslop, P. St., Dobson, C. M. & Klenerman, D. (2013). Single molecule characterization of the interactions between amyloid-β peptides and the membranes of hippocampal cells. Journal of the American Chemical Society, 135 (4), 1491-1498.

Scopus Eid


  • 2-s2.0-84873809834

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1321&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/309

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 1491

End Page


  • 1498

Volume


  • 135

Issue


  • 4

Place Of Publication


  • United States