Cholesterol modulates the interaction of beta-amyloid peptide with lipid bilayers.

Abstract:

: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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Qiu L,Lewis A,Como J,Vaughn MW,Huang J,Somerharju P,Virtanen J,Cheng KH

doi

10.1016/j.bpj.2009.02.036

subject

Has Abstract

pub_date

2009-05-20 00:00:00

pages

4299-307

issue

10

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(09)00595-5

journal_volume

96

pub_type

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