Cholesterol modulates the interaction of beta-amyloid peptide with lipid bilayers.
The interaction of an amphiphilic, 40-amino acid beta-amyloid (Abeta) peptide with liposomal membranes as a function of sterol mole fraction (X(sterol)) was studied based on the fluorescence anisotropy of a site-specific membrane sterol probe, dehydroergosterol (DHE), and fluorescence resonance energy transfer (FRET) from the native Tyr-10 residue of Abeta to DHE. Without Abeta, peaks or kinks in the DHE anisotropy versus X(sterol) plot were detected at X(sterol) approximately 0.25, 0.33, and 0.53. Monomeric Abeta preserved these peaks/kinks, but oligomeric Abeta suppressed them and created a new DHE anisotropy peak at X(sterol) approximately 0.38. The above critical X(sterol) values coincide favorably with the superlattice compositions predicted by the cholesterol superlattice model, suggesting that membrane cholesterol tends to adopt a regular lateral arrangement, or domain formation, in the lipid bilayers. For FRET, a peak was also detected at X(sterol) approximately 0.38 for both monomeric and oligomeric Abeta, implying increased penetration of Abeta into the lipid bilayer at this sterol mole fraction. We conclude that the interaction of Abeta with membranes is affected by the lateral organization of cholesterol, and hypothesize that the formation of an oligomeric Abeta/cholesterol domain complex may be linked to the toxicity of Abeta in neuronal membranes.
Qiu
Liming
L
Department of Physics, Texas Tech University, Lubbock, Texas, USA.
Lewis
Anthony
A
Como
John
J
Vaughn
Mark W
MW
Huang
Juyang
J
Somerharju
Pentti
P
Virtanen
Jorma
J
Cheng
Kwan Hon
KH
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D004875:Ergosterol / Q000031:analogs & derivatives / Q000378:metabolism; D005454:Fluorescence Polarization; D031541:Fluorescence Resonance Energy Transfer; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C010905:dehydroergosterol; D014443:Tyrosine; D002784:Cholesterol; D004875:Ergosterol