For lipids like phosphatidylcholines the gradients in dynamic properties along the molecular segments of the acyl chains and the headgroup are relatively well characterized, 22,23 whereas mixtures including gangliosides are far less investigated. Lipid membranes exhibit a range of dynamics on different time scales, 21 such as librations, trans-gauche isomerism and rotational and lateral diffusion. The composition of lipid membranes affects their self-assembly behavior with implications for dynamics, structure and lateral heterogeneity. It is the major ganglioside type in mammalian heart, skeletal muscle, kidney, liver and adipose tissue 14,16 and has been linked to insulin resistance, 17 diabetes, 18 cancer 19 and neuronal cell death. 15 The headgroup of GM3 is a three sugar-units long oligosaccharide, including a negatively charged NeuAc residue ( Fig.

12–15 Ganglioside GM3 is one of the simpler gangliosides, from which the major brain gangliosides GM1, GD1a, GD1b and GT1b are biosynthesized. These types of lipids are mainly located in the outer leaflet of the plasma membrane and are particularly concentrated (up to 10 wt%) in neurons, 10 where they have been suggested to have important roles in neuronal development and function, 11 modulation of cell-surface interactions and cell signalling. Gangliosides are glycosphingolipids that contain sialic acid, most commonly N-acetylneuraminic acid (NeuAc) in humans 9 and ceramide (Cer) as their hydrophobic part. 1 Chemical structures and carbon labels for (A) GM3 and (B) POPC lipid molecules. As an example, glycolipid-containing membranes have previously been shown to interfere with the process of amyloid formation for different amyloid-forming proteins. 6 The formation of such clusters may in turn be crucial for the interactions between the membrane and macromolecules in the membrane surroundings. 4 The headgroup structure of glycolipids enables strong inter-headgroup interactions, 5 which can lead to the formation of clusters with in-plane dimensions on the 10–100 nm length scale. The chemical properties of lipids such as headgroup size and charge, hydrophobic chain length and degree of unsaturation affect lipid self-assembly 2 and may have consequences for the function of integral membrane proteins 3 and how peripheral membrane proteins interface with the membrane surface. 1) that typically contain glucose (Glc) and galactose (Gal) residues with different linkages and substitutions. Glycolipids are lipids with carbohydrate headgroups ( Fig. 1 With respect to the lipid components, the evolution has led to a great chemical diversity of the major lipid classes in mammals cells, including glycerophospholipids, glycolipids and sterols, each of them promoting different membrane structures and targets for interactions with biomolecules in the membrane environment. Both composition and structure vary largely between different cellular organelles and even between the inner and outer leaflets of the cellular membranes. Introduction Cell membranes are very complex biological assemblies composed of a large variety of lipids, proteins and carbohydrates. Our results revealed that all C–H segments of POPC reorient slower in the presence of GM3 and that the defining features of the GM3-POPC bilayer lie in the GM3 headgroup it gives the bilayer an extended headgroup layer with high order (| S CH| up to 0.3–0.4) and slow dynamics ( τ e up to 100 ns), a character that may be mechanistically important in ganglioside interactions with other biomolecules. These two methods yield reorientational correlation functions, molecular profiles of C–H bond order parameters | S CH| and effective correlation times τ e, which we compare for lipids in POPC bilayers with and without 30 mol% GM3. We combine solid-state NMR spectroscopy with all-atom molecular dynamics (MD) simulations to investigate how ganglioside GM3 affects the bilayer structure and dynamics of C–H bond segments.

To better understand how the properties of individual lipid molecules can contribute to shape the functional aspects of a membrane, the spatial restriction and dynamics of C–H bond segments can be measured using nuclear magnetic resonance (NMR) spectroscopy. Glycolipids such as gangliosides affect the properties of lipid membranes and in extension the interactions between membranes and other biomolecules like proteins.

Density of water gm3