Cholesterol transfer between lipid vesicles. Effect of phospholipids and gangliosides

Abstract

The effect of lipid composition on the rate of cholesterol movement between cellular membranes is investigated using lipid vesicles. The separation of donor and acceptor vesicles required for rate measurement is achieved by differential centrifugation so that the lipid effect can be quantified in the absence of a charged lipid generally used for ion-exchange-based separation. The rate of cholesterol transfer from small unilamellar vesicles (SUVs) containing 50 mol% cholesterol to a common large unilamellar vesicle (LUV) acceptor containing 20 mol% cholesterol decreases with increasing mol% of sphingomyelin in the SUVs, while phosphatidylethanolamine and phosphatidylserine have no appreciable effect at physiologically relevant levels. There is a large decrease in rate when phosphatidylethanolamine constitutes 50 mol% of donor phospholipids. Interestingly, gangliosides which have the same hydrocarbon moiety as sphingomyelin exert an opposite effect. The effect of spingomyelin seems to be mediated by its ability to decrease the fluidity of the lipid matrix, while that of gangliosides may arise from a weakening of phosphatidylcholine-cholesterol interactions or from a more favourable (less polar) microenvironment for the desorption of cholesterol provided by the head-group interactions involving sugar residues. If the effect of asymmetric transbilayer distribution of lipids is taken into consideration, the observed composition-dependent rate changes could partly account for the large difference in the rates of cholesterol desorption from the inner and outer layers of plasma membrane. Such rate differences may be responsible for an unequal steady-state distribution of cholesterol among various cellular membranes and lipoproteins.

Sphingolipid Storage Induces Accumulation of Intracellular Cholesterol by Stimulating SREBP-1 Cleavage

“…The converse situation, in which SM depletion by sphingomyelinase treatment leads to increased cholesterol translocation to the ER and a subsequent suppression of SREBP cleavage, has also been reported (32). Our model is in agreement with many observations in the literature showing interactions of SLs with cholesterol in various model and natural membrane systems (33)(34)(35)(36)(37). The "strength" of the interaction between cholesterol and different SLs could influence the reduction in free cholesterol in the cell and thus explain the variations seen in cellular cholesterol levels (Table I) and LDL R expression (Fig.…”

Spontaneous lipid transfer between organized lipid assemblies

“…By studying the influence of cholesterol/PC ratio of the donor bilayer, these investigators found the rate of cholesterol desorption to be consistent with a model in which cholesterol desorbs from that fraction of the bilayer surface which is covered by an equimolear cluster of cholesterol and PC [67]. In subsequent studies, various laboratories have continued to probe how bilayer composition affects cholesterol exchange rates [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84]. All reports agree that membrane composition plays a critical role in regulating cholesterol exchange and that sphingomyelin, in particular, slows cholesterol exchange rates.…”

Transmembrane Peptides Influence the Affinity of Sterols for Phospholipid Bilayers

“…The affinity of sterols for lipid bilayers has been measured successfully previously by measuring how sterols partition between cyclodextrins and lipid bilayers (21)(22)(23)(24)26). In the majority of these studies, 3 H-cholesterol was used as a probe, and in two studies cholesterol partitioning was measured using isothermal titration calorimetry. A draw back in all the methods used previously is that rather large quantities of material is needed, and that relatively high cholesterol concentrations were used to keep the phospholipid concentrations lower.…”

“…How the lateral organization of a phospholipid bilayer is influenced by cholesterol depends on the phospholipid composition of the bilayer. Cholesterol has been shown to interact differently with different phospholipid types (1)(2)(3), and to prefere phospholipids with saturated acyl chains over those with unsaturated chains (see (4) and references within). Hence, cholesterol can facilitate lateral separation in complex bilayer membranes by favoring saturated acyl chains over unsaturated ones.…”