Abstract
Ganglioside lipids have been associated with several physiological processes, including cell signaling. They have also been associated with amyloid aggregation in Parkinson’s and Alzheimer’s disease. In biological systems, gangliosides are present in a mix with other lipid species, and the structure and properties of these mixtures strongly depend on the proportions of the different components. Here, we study self-assembly in model mixtures composed of ganglioside GM1 and a zwitterionic phospholipid, 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC). We characterize the structure and molecular dynamics using a range of complementary techniques, including cryo-TEM, polarization transfer solid state NMR, diffusion NMR, small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and calorimetry. The main findings are: (1) The lipid acyl chains are more rigid in mixtures containing both lipid species compared to systems that only contain one of the lipids. (2) The system containing DOPC with 10 mol % GM1 contains both vesicles and micelles. (3) At higher GM1 concentrations, the sample is more heterogenous and also contains small disc-like or rod-like structures. Such a co-existence of structures can have a strong impact on the overall properties of the lipid system, including transport, solubilization, and partitioning, which can be crucial to the understanding of the role of gangliosides in biological systems.
Highlights
Ganglioside lipids have been associated with several physiological processes, including cell signaling, neuronal recovery and protection, and apoptosis [1,2,3]
We have previously demonstrated that ganglioside-containing exosomes, as well as vesicles prepared from extracted exosome lipids and ganglioside-containing model mixtures, accelerate the amyloid formation of α-synuclein, which is related to Parkinson’s disease [8]
The mixing of different lipid species may lead to the formation of new structures with altered properties that cannot be achieved by the single components
Summary
Ganglioside lipids have been associated with several physiological processes, including cell signaling, neuronal recovery and protection, and apoptosis [1,2,3]. In GM1-rich systems, (mixed) micelles will form, while planar bilayers will be formed in phospholipid-rich systems On thermodynamic grounds, it follows that for GM1-phospholipid mixtures with compositions in between those extreme cases where only one type of structure is present, the sample will be heterogenous and contain two or more co-existing structures. It follows that for GM1-phospholipid mixtures with compositions in between those extreme cases where only one type of structure is present, the sample will be heterogenous and contain two or more co-existing structures Such heterogeneity will have a strong impact on the overall properties of the lipid system, including the transport properties, solubilization of hydrophobic species, partitioning of interacting molecules between the different assemblies, relaxation rates, aggregate curvature, etc. This co-existence is highly relevant in terms of physiological ganglioside contents
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