Sphingolipid partitioning into ordered domains in cholesterol-free and cholesterol-containing lipid bilayers.
We have used fluorescence-quenching measurements to characterize the partitioning of a variety of indolyl-labeled phospho- and sphingolipids between gel or liquid-ordered and liquid-disordered lipid domains in several types of lipid bilayers where such domains coexist. In both cholesterol-free and cholesterol-containing lipid mixtures, sphingolipids with diverse polar headgroups (ranging from sphingomyelin and monoglycosylceramides to ganglioside GM1) show a net preference for partitioning into ordered domains, which varies modestly in magnitude with varying headgroup structure. The affinities of different sphingolipids for ordered lipid domains do not vary in a consistent manner with the size or other simple structural properties of the polar headgroup, such that for example ganglioside GM1 partitions between ordered and disordered lipid domains in a manner very similar to sphingomyelin. Ceramide exhibits a dramatically higher affinity for ordered lipid domains in both cholesterol-free and cholesterol-containing bilayers than do other sphingolipids. Our findings suggest that sphingolipids with a variety of headgroup structures will be enriched by substantial factors in liquid-ordered versus liquid-disordered regions of membranes, in a manner that is only modestly dependent on the nature of the polar headgroup. Ceramide is predicted to show a very strong enrichment in such domains, supporting previous suggestions that ceramide-mediated signaling may be compartmentalized to liquid-ordered (raft and raft-related) domains in the plasma membrane.
Wang
Tian-Yun
TY
Department of Biochemistry, McGill University, Montréal, Québec, Canada H3G 1Y6.
Silvius
John R
JR
D002518:Ceramides / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry*; D005782:Gels / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D046911:Macromolecular Substances; D008560:Membrane Fluidity; D021962:Membrane Microdomains / Q000737:chemistry*; D008567:Membranes, Artificial; D008968:Molecular Conformation; D012996:Solutions / Q000737:chemistry; D013050:Spectrometry, Fluorescence / Q000379:methods*; D013107:Sphingolipids / Q000737:chemistry*
D002518:Ceramides; D005782:Gels; D008051:Lipid Bilayers; D046911:Macromolecular Substances; D008567:Membranes, Artificial; D012996:Solutions; D013107:Sphingolipids; D002784:Cholesterol