Amyloid β-peptide insertion in liposomes containing GM1-cholesterol domains
Maria Carmela Nicastro1, Dario Spigolon2, Fabio Librizzi3
1National Research Council, Institute of Biostructure and Bioimaging, Via Gaifami 18, Catania, Italy.
Abstract:
Neuronal membrane damage is related to the early impairments appearing in Alzheimer's disease due to the interaction of the amyloid β-peptide (Aβ) with the phospholipid bilayer. In particular, the ganglioside GM1, present with cholesterol in lipid rafts, seems to be able to initiate Aβ aggregation on membrane. We studied the thermodynamic and structural effects of the presence of GM1 on the interaction between Aβ and liposomes, a good membrane model system. Isothermal Titration Calorimetry highlighted the importance of the presence of GM1 in recruiting monomeric Aβ 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 Aβ. The results suggest that the interaction with GM1 brings to insertion of Aβ in the bilayer, producing a structural perturbation down to the internal layers of the liposome, as demonstrated by the obtained electron density profiles.
Insights
Ganglioside GM1 initiates amyloid beta-peptide (Aβ) aggregation on neuronal membranes in Alzheimer's disease. GM1 recruits Aβ to lipid bilayers, causing structural damage and internal liposome perturbations.
Area of Science:
- Neuroscience
- Biochemistry
- Materials Science
Background:
- Neuronal membrane damage is an early indicator in Alzheimer's disease (AD).
- Amyloid beta-peptide (Aβ) interaction with phospholipid bilayers contributes to this damage.
- Ganglioside GM1, found in lipid rafts with cholesterol, may initiate Aβ aggregation on membranes.
Purpose of the Study:
- To investigate the thermodynamic and structural effects of GM1 on Aβ-liposome interactions.
- To understand GM1's role in Aβ aggregation and membrane perturbation.
Main Methods:
- Liposomes were used as a model membrane system.
- Isothermal Titration Calorimetry (ITC) was employed to study Aβ recruitment.
- Light Scattering and Small Angle X-ray Scattering (SAXS) were used to analyze structural changes.
Main Results:
- ITC confirmed GM1's role in recruiting monomeric Aβ to the lipid bilayer.
- GM1-containing liposomes exhibited distinct scattering patterns before and after Aβ interaction.
- Electron density profiles indicated Aβ insertion into the bilayer and structural perturbation.
Conclusions:
- GM1 plays a crucial role in initiating Aβ interaction with and aggregation on neuronal membranes.
- The presence of GM1 leads to significant structural alterations within the lipid bilayer upon Aβ binding.
- These findings provide insights into the early mechanisms of membrane damage in Alzheimer's disease.
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