Journal
FEBS JOURNAL
Volume 273, Issue 7, Pages 1389-1402Publisher
WILEY
DOI: 10.1111/j.1742-4658.2006.05162.x
Keywords
Alzheimer's disease; amyloid toxicity; microdomains; plasmon-waveguide resonance spectroscopy; rafts
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Funding
- NIGMS NIH HHS [GM 59630] Funding Source: Medline
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We utilized plasmon-waveguide resonance (PWR) spectroscopy to follow the effects of sphingomyelin.. cholesterol and zinc ions on the binding and aggregation of the amyloid beta peptide(1-40) in lipid bilayers. With a dioleoylphosphatidylcholine (DOPC) bilayer, peptide binding was observed, but no aggregation Occurred over a period of 15 h. In contrast, similar binding was found with a brain sphingomyelin (SM) bilayer, but in this case an exponential aggregation process was observed during the same time interval. When the SM bilayer included 35% cholesterol.. an increase of approximate to 2.5-fold occurred in the amount of peptide bound,. with a similar increase in the extent of aggregation, the latter resulting in decreases in the bilayer packing density and displacement of lipid. Peptide association with a bilayer formed from equimolar amounts of DOPC, SM and cholesterol was followed using a high-resolution PWR sensor that allowed microdomains to be observed. Biphasic binding to both domains occurred, but predominantly to the SM-rich domain, initially to the surface and at higher peptide concentrations within the interior of the bilayer. Again,. aggregation was observed and Occurred within both microdomains, resulting in lipid displacement. We attribute the aggregation in the DOPC-enriched domain to be a consequence of lipid mixing within these microdomains, resulting in the presence of small amounts of SM and cholesterol in the DOPC microdomain. When 1 mM zinc was present, an increase of approximately threefold in the amount of peptide association was observed, as well as large changes in mass and bilayer structure as a consequence of peptide aggregation, occurring without loss of bilayer integrity. A structural interpretation or peptide interaction with the bilayer is presented based on the results of simulation analysis of the PWR spectra.
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