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- Mikhalyov, I, et al.
(författare)
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Designed fluorescent probes reveal interactions between Amyloid-β(1-40) Peptides and GM1 Gangliosides in Micelles and Lipid Vesicles
- 2010
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 99:5, s. 1510-1519
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Tidskriftsartikel (refereegranskat)abstract
- A hallmark of the common Alzheimer's disease (AD) is the pathological conversion of its amphiphatic amyloid-beta (Abeta) peptide into neurotoxic aggregates. In AD patients, these aggregates are often found to be tightly associated with neuronal G(M1) ganglioside lipids, suggesting an involvement of G(M1) not only in aggregate formation but also in neurotoxic events. Significant interactions were found between micelles made of newly synthesized fluorescent G(M1) gangliosides labeled in the polar headgroup or the hydrophobic chain and Abeta(1-40) peptide labeled with a BODIPY-FL-C1 fluorophore at positions 12 and 26, respectively. From an analysis of energy transfer between the different fluorescence labels and their location in the molecules, we were able to place the Abeta peptide inside G(M1) micelles, close to the hydrophobic-hydrophilic interface. Large unilamellar vesicles composed of a raftlike G(M1)/bSM/cholesterol lipid composition doped with labeled G(M1) at various positions also interact with labeled Abeta peptide tagged to amino acids 2 or 26. A faster energy transfer was observed from the Abeta peptide to bilayers doped with 581/591-BODIPY-C(11)-G(M1) in the nonpolar part of the lipid compared with 581/591-BODIPY-C(5)-G(M1) residing in the polar headgroup. These data are compatible with a clustering process of G(M1) molecules, an effect that not only increases the Abeta peptide affinity, but also causes a pronounced Abeta peptide penetration deeper into the lipid membrane; all these factors are potentially involved in Abeta peptide aggregate formation due to an altered ganglioside metabolism found in AD patients.
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- Mikhalyov, I, et al.
(författare)
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Donor-donor energy migration (DDEM) as a tool for studying aggregation in lipid phases
- 2001
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Ingår i: SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR. - 1386-1425. ; 57:9, s. 1839-45
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Tidskriftsartikel (refereegranskat)abstract
- A BODIPY(R)-labelled sulfatide (N-(BODIPY(R)- FL-pentanoyl) -galactosylcerebroside-sulfate, hereafter abbreviated as BD-Sulfatide) was solubilised at different concentrations in lipid vesicles of 1,2-dioleoyl-sn -glycero-3-phosphocholine (DOPC). Time-correlated single photon counting experiments show that the fluorescence relaxation is mono-exponential (with a lifetime of 6.5 ns) at molar ratios of BD-Sulfatide: DOPC that are less than 1:100. The fluorescence steady-state anisotropy decreases monotonously at molar ratios smaller than 1:1000, which is compatible with donor-donor energy migration (DDEM) among the BODIPY(R) groups. A model that assumes DDEM across the lipid bilayers, as well as in their planes, was used to analyse the time-resolved fluorescence anisotropy. Only two parameters appear in the model namely; the bilayer thickness (d) and the average number density (C-2) distribution of BD-Sulfatide in the lipid bilayers. The extracted d-values vary between 35 and 40 Angstrom, which is about the reported thickness of a bilayer of DOPC (38 Angstrom). Hence, the BODIPY(R) groups are preferentially located in the water-lipid interface. At low concentration the experimental C-2-values and those independently calculated are in good agreement, while the experimental values gradually become lower with increasing BD-Sulfatide concentration. These results are compatible with an aggregation of the sulfatides and self-quenching of BODIPY(R), which is clearly established at higher concentrations of the BD-Sulfatide.
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