Bilayer structure of ganglioside/cholesterol mixed system in the presence of Ca²⁺

Abstract

We employed small-angle X-ray scattering measurement using synchrotron radiation to study structural properties of monosialoganglioside (G M1 )/cholesterol (chol) mixtures in aqueous dispersions, in the presence of 0 -50 mM CaCl 2 . Various molar ratios of G M1 /chol were examined from 1:0 to 1:5. Without CaCl 2 the radius of gyration (R g ) of the aggregate increased linearly with increasing cholesterol content up to G M1 /chol=1/1. At cholesterol content above G M1 /chol=1/1, R g of the aggregate was almost constant, and a sharp diffraction peak at q=0.18 Å -1 , characteristic of cholesterol monohydrate crystals, was observed, suggesting the solubility limit of cholesterol in G M1 aggregates is about G M1 /chol=1/1.For the samples containing cholesterol of G M1 /chol=1/0.6 and above, the diffraction patterns showed a set of peaks that correspond to ~85 Å periodic lamellar structures in the presence of CaCl 2 at concentrations higher than ~10 mM. The observed lamellar peak positions and the intensity ratio of the lamellar peaks (1st -4th) was not changed by the addition of CaCl 2 up to 100 mM, demonstrating once formed multilayered structure of G M1 /chol was not altered under the present conditions. Electron density profiles for this G M1 /chol bilayer were obtained. The Ca 2+induced vesicle-to-lamellar phase separation of this system was found to be highly reversible by the Ca 2+ chelation with ethylenediamine-tetraacetic acid.

Effect of Protein-Encapsulation on Thermal Structural Stability of Liposome Composed of Glycosphingolipid/Cholesterol/Phospholipid

“…DPPC and egg-PC were purchased from Avanti Polar Lipids, Inc. (USA). Gangliosides were extracted and separated from bovine brain by the method described elsewhere . The encapsulated protein was myoglobin from horse skeletal muscle (SIGMA).…”

“…25 Neutron spin-echo studies suggest that gangliosides can affect and/or control diffusional motions (undulation/bending motions) of micelles and liposomes. [22][23][24][25][26] In addition, the specific interaction between ganglioside and protein (amyloid beta protein (Aβ1-40)) significantly changes the diffusional bending motion of liposomes. 27 The above characteristics of gangliosides would not only show the biological functions as lipid-rafts' components, but also indicate the usefulness for developing a new type of liposome DDS.…”

“…We have found various notable characteristics of ganglioside molecules as summarized below. Reversible hydration–dehydration of the sugar-head region depending on temperature, which accompanies the change of dissociation degree of sialic acids, − the presence of maximum miscibility of cholesterol molecules against gangliosides, micelle-to-vesicle transition depending on cholesterol content, reversible transition from vesicle to lamellar induced by Ca 2+ ions, and so on. The liposomes containing gangliosides take an asymmetric lipid-bilayer structure in which gangliosides localize preferentially at the outer-leaflet of the liposomes, and the microdomains being rich in gangliosides and cholesterol change those heterogeneous distributions in the liposome surface sensitively against temperature variation .…”

Functional Properties of Glycosphingolipid Aggregates and Mixtures with Cholesterol and Phospholipid

“…In ganglioside (GM 1 )/phospholipid (DPPC, dipalmitoyl phosphocholine) mixed small unilamellar vesicle (SUV) system gangliosides predominantly locate at outer-leaflet of the vesicle as occurring in plasma membrane [20]. 3) In the cases of ganglioside (GMb Gm., Gmb, Gnb)-cholesterol binary systems (monosialoganglioside, GM 1 ; disialoganglioside, Gm., IV 3 NeuAc-, IeNeuAc-GgOse4-Cer; disialoganglioside, Gmb, II 3 NeuAc 2 -GgOse 4 -Cer; trisialoganglioside, GT 1 b, IV 3 NeuAc-, II 3 NeuAcrGg0se 4 -Cer) we found the presence of maximum miscibility of cholesterols within gangliosides, the cholesterol-dependent micelle-tovesicle transitions (GMJ), and the Ca-induced vesicle-tolamellar transitions (GM 1 ) accompanying the formation of an interdigitated structure between the sugar heads in the opposing bilayers [21]. 4) From the NSE experiments, the dehydration and the bending of sugar heads suppress the undulation of the ganglioside micellar structure [22].…”

Effect of Alcohols on Glycosphingolipid Aggregates

“…2) Predominantly location of gangliosides at outer-leaflet of ganglioside-phospholipid vesicles [18,19]. 3) Presence of maximum miscibility of cholesterols to gangliosides in ganglioside-cholesterol binary mixtures; cholesterol-dependent micelle-to-vesicle and ea-induced vesicle-to-lamellar transitions with the formation of interdigitated structures between oligosaccharide chains [20,21]. 4) Dynamics of ganglioside micelles and ganglioside-cholesterolphospholipid ternary mixtures dominated by hydration and bending of oligosaccharide chains; smallest values at the lipid composition as similar as in intact membrane 567 including rafts [21,22].…”