Influence of the Linkage Region of Sphingolipids on Sphingolipid−Phospholipid Mixing in Cholesterol-Rich Bilayers^†

The influence of the linkage region of a sphingolipid on its mixing with a phospholipid in cholesterol-rich bilayers has been examined by use of the nearest-neighbor recognition method (Davidson, S. K. M.; Regen, S. L. Chem. Rev. 1997, 97, 1269). Thus, an analysis of equilibrium dimer distributions derived from an exchangeable sphingolipid monomer (SL, made from N-stearoyl-d-erythro-sphinganine) or a phospholipid analogue (PL, made from 1-myristoyl-2-stearoyl-sn-glycero-3-phosphoethanolamine) plus a shorter phospholipid (14, made from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine) has revealed a preference for homolipid association in SL/14-based bilayers; that is, the linkage region of the sphingolipid promotes its segregation from the phospholipid. Inclusion of 20−40 mol % cholesterol increases this preference for homolipid association. The magnitude of this effect is similar to that found in cholesterol-rich bilayers containing two exchangeable phospholipids, which differ in length by four methylene units, that is, 18 (made from 1,2-distearoyl-sn-glycero-3-phosphoethanolamine) and 14. The relevance of these findings to the concept of lipid rafts is briefly discussed

Influence of the Linkage Region of Sphingolipids on Sphingolipid−Phospholipid Mixing in Cholesterol-Rich Bilayers^†

The influence of the linkage region of a sphingolipid on its mixing with a phospholipid in cholesterol-rich bilayers has been examined by use of the nearest-neighbor recognition method (Davidson, S. K. M.; Regen, S. L. Chem. Rev. 1997, 97, 1269). Thus, an analysis of equilibrium dimer distributions derived from an exchangeable sphingolipid monomer (SL, made from N-stearoyl-d-erythro-sphinganine) or a phospholipid analogue (PL, made from 1-myristoyl-2-stearoyl-sn-glycero-3-phosphoethanolamine) plus a shorter phospholipid (14, made from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine) has revealed a preference for homolipid association in SL/14-based bilayers; that is, the linkage region of the sphingolipid promotes its segregation from the phospholipid. Inclusion of 20−40 mol % cholesterol increases this preference for homolipid association. The magnitude of this effect is similar to that found in cholesterol-rich bilayers containing two exchangeable phospholipids, which differ in length by four methylene units, that is, 18 (made from 1,2-distearoyl-sn-glycero-3-phosphoethanolamine) and 14. The relevance of these findings to the concept of lipid rafts is briefly discussed

Is the Linkage Region of Sphingolipids Responsible for Lipid Raft Formation?

Is the Linkage Region of Sphingolipids Responsible for Lipid Raft Formation

The Structural Role of Cholesterol in Biological Membranes

The Structural Role of Cholesterol in Biological Membrane

The Importance of Acyl Chain Placement on Phospholipid Mixing in the Physiologically Relevant Fluid Phase

The Importance of Acyl Chain Placement on Phospholipid Mixing in the Physiologically Relevant Fluid Phas

Sugar-Based Lipid Headgroups: How Sticky Are They?

This paper reports the synthesis of a disulfide-based exchangeable glycophospholipid and establishes that this lipid mixes, ideally, with a shorter-chain, phospholipid analogue in cholesterol-rich fluid bilayers. These findings indicate that associative interactions between carbohydrate headgroups are unlikely to provide a significant driving force for the clustering of glycolipids in biological membranes