insertion in liposomes containing GM1-cholesterol domains

Neuronal membrane damage is related to the early impairments appearing in Alzheimer's disease. The interaction of the amyloid ?-peptide (A?) with the phospholipid bilayer could onset pathological mechanisms. Both aberrant A? species and membrane components could play a role in promoting aggregation, deposition and signal dysfunction. The ganglioside GM1, present with cholesterol in lipid rafts, seems to be able to initiate A? aggregation on membrane. [1] Liposomes can be used as a model system to gain information on such an interaction. Here, we have studied by a thermodynamic and structural point of view the effect of GM1 embedded in liposomes on the interaction with A?. Liposomes (LUV, PC:PS:Chol, 8:1:1 in mass) were prepared in the absence or presence of GM1 (5% wt). Isothermal Titration Calorimetry experiments carried out at 25°C have highlighted the importance of the presence of GM1, concerted with cholesterol, in recruiting freshly-dissolved monomeric A? toward the lipid bilayer. Light and Small Angle X-ray Scattering have been used to characterize the systems under study, reporting a different pattern just in the case of GM1 containing liposomes, before and after interaction with A?. Results suggest that the interaction, which is mainly electrostatically driven, brings to insertion of the peptide in the bilayer producing a structural perturbation deeply in the inner layer of the liposome containing GM1, as demonstrated by the data fitting electron density profile.