title: Lipid domains in the membrane: thermotropic properties of sphingomyelin vesicles containing GM1 ganglioside and cholesterol.
abstract: The thermotropic behavior of palmitoylsphingomyelin vesicles containing GM1 ganglioside and cholesterol has been investigated by high-sensitivity differential scanning calorimetry. The thermograms exhibited by binary palmitoylsphingomyelin/GM1 mixtures are resolvable into two components. The relative contribution of the minor component, undetectable in the absence of ganglioside, to the total enthalpy and its transition temperature (>40 degrees C) increase with the concentration of the glycolipid embedded in the vesicles. These data suggest the occurrence of lateral phase separation and that more ordered, higher melting GM1 ganglioside-enriched domains are present within the sphingomyelin bilayer. Studies on binary sphingomyelin/cholesterol mixtures confirmed the known tendency of the sterol to decrease the total enthalpy of sphingomyelin, forming cholesterol-enriched domains. The thermograms exhibited by ternary sphingomyelin/ganglioside/cholesterol mixtures in variable proportions (up to 20% molar GM1 or Chol) displayed, on increasing the content of either the sterol or the ganglioside, features addressable to sphingomyelin/cholesterol (peaks centered at temperature </=40 degrees C, decrease of enthalpy) or to sphingomyelin/GM1 mixtures (peaks centered at a temperature >40 degrees C), respectively. This trend was confirmed by deconvolution analysis, showing that the thermograms are resolvable into components addressable to GM1-enriched and to cholesterol-enriched domains. Taken all together, the results show that the architectural features of sphingomyelin bilayers are strongly dependent on the presence of GM1 ganglioside and cholesterol, whose presence is leading to the formation of separate, GM1-enriched and cholesterol-enriched distinct domains. Ganglioside-sphingomyelin and sphingomyelin-cholesterol, together with mutual ganglioside-ganglioside, interactions could contribute to maintain a network of bonds extending to proteins, forming specialized membrane domains, such as caveolae, or others, whose experimental clues are the glycolipid-enriched detergent-insoluble fractions that can be isolated from cell membranes.
authors.affiliation: Department of Medical Chemistry and Biochemistry, University of Milan, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ferraretto
authors.forename: M
authors.initials: M
authors.lastname: Pitto
authors.forename: P
authors.initials: P
authors.lastname: Palestini
authors.forename: M
authors.initials: M
authors.lastname: Masserini
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002417:Cattle; D002784:Cholesterol / Q000737:chemistry*; D005677:G(M1) Ganglioside / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes; D013109:Sphingomyelins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D013109:Sphingomyelins; D005677:G(M1) Ganglioside; D002784:Cholesterol