4.4 Article

Amyloid β-peptide insertion in liposomes containing GM1-cholesterol domains

Journal

BIOPHYSICAL CHEMISTRY
Volume 208, Issue -, Pages 9-16

Publisher

ELSEVIER
DOI: 10.1016/j.bpc.2015.07.010

Keywords

A beta-membrane interaction; Double layer perturbation; Small angle X-ray scattering; Isothermal titration calorimetry

Funding

  1. FIRB [RBNE08HWLZ MERIT, RBFR12SIPT MIND]

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Neuronal membrane damage is related to the early impairments appearing in Alzheimer's disease due to the interaction of the amyloid beta-peptide (A beta) with the phospholipid bilayer. In particular, the ganglioside GM1, present with cholesterol in lipid rafts, seems to be able to initiate A beta aggregation on membrane. We studied the thermodynamic and structural effects of the presence of GM1 on the interaction between A beta and liposomes, a good membrane model system. Isothermal Titration Calorimetry highlighted the importance of the presence of GM1 in recruiting monomeric A beta toward the lipid bilayer. Light and Small Angle X-ray Scattering revealed a different pattern for GM1 containing liposomes, both before and after interaction with A beta. The results suggest that the interaction with GM1 brings to insertion of A beta in the bilayer, producing a structural perturbation down to the internal layers of the liposome, as demonstrated by the obtained electron density profiles. (C) 2015 Elsevier B.V. All rights reserved.

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