Cholesterol desorption from clusters of phosphatidylcholine and cholesterol in unilamellar vesicle bilayers during lipid transfer or exchange

McLean, Larry R.; Phillips, Michael C.

doi:10.1021/bi00260a022

Cited by 74 publications

(37 citation statements)

References 42 publications

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“…The data fitted the equation with correlation coefficients (r2) in the range of 0.960-0.999 (most of them > 0.99), but gave a small intercept in almost all cases, indicating an initial much faster phase comprising 10-15 % of the total reaction, as we have noticed in other systems as well (Thomas & Poznansky, 1988). A similar rapid initial phase had also been reported previously (McLean & Phillips, 1982;Lange et al, 1983). Refitting the data with the 15 min point as t = 0 also gave a good fit (r2 = 0.970-0.999, most of them > 0.99), but with intercepts very close to zero.…”

Section: Vesicle Diametersupporting

confidence: 88%

Effect of surface curvature on the rate of cholesterol transfer between lipid vesicles

Thomas

Poznansky

1988

Biochemical Journal

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The effect of surface curvature on the spontaneous movement of cholesterol between membranes was investigated by measuring the rates of cholesterol transfer from donor vesicles of various sizes to a common acceptor vesicle. Donor vesicles of size in the range 40-240 nm were prepared by extruding multilamellar dispersions through polycarbonate filters of different pore sizes under pressure. The smallest donor vesicle and the acceptor vesicles were obtained by the normal sonication procedures. The rate of cholesterol transfer, as measured by the movement of [3H]cholesterol, decreases with increasing size of the donor vesicle in an almost linear fashion. The extrapolation of the results gave a half-time (t1/2) of 16-20 h of the desorption of cholesterol from a planar bilayer, and this can be considered as a reference value for most cellular membranes which are characterized by very low curvatures. Our earlier studies have shown that the t1/2 for cholesterol efflux is influenced by the presence of gangliosides and phosphatidylethanolamine, and the asymmetric distribution of these lipids in the plasma membrane could partially account for the large difference in the rates of cholesterol movement from the two sides of the plasma membrane. The small differences in rates arising from asymmetric distribution will be magnified by the longer t1/2 obtained here for membranes of low curvatures, so that the large difference in rates might be a coupled effect of lipid asymmetry and low curvature of the plasma membrane. This, in turn, may have a role in maintaining the large differences in cholesterol/phospholipid molar ratios observed between plasma membrane and intracellular membranes.

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Section: Vesicle Diametersupporting

confidence: 88%

Effect of surface curvature on the rate of cholesterol transfer between lipid vesicles

Thomas

Poznansky

1988

Biochemical Journal

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“…An initial fast phase of 10-15 % was observed when the ionexchange method was used to separate the donor and acceptor vesicles and also when purified (> 9900) [3H]cholesterol was used. McLean & Phillips (1982) have observed a similar fast component accounting for 9 % of the cholesterol transferred when a 1:3.4 DPPC/ cholesterol dispersion was incubated with PC vesicles containing 15 mol dicetyl phosphate. The authors have suggested that the rapid initial phase may be due to loosely absorbed cholesterol molecules on the vesicle surface.…”

Section: Discussionmentioning

confidence: 64%

Cholesterol transfer between lipid vesicles. Effect of phospholipids and gangliosides

Thomas

Poznansky

1988

Biochemical Journal

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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.

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“…Membrane lipid transfer systems are generally characterized by a high energy of activation, ascribed to the insolubility of monomers in the aqueous space (McLean and Phillips, 1984;Nichols, 1985;Phillips et al, 1987). Typical activation energies for cholesterol transfer are 10 -20 Kcal/mol or more (Jonas and Maine, 1979;Poznansky and Czekanski, 1979;Gottlieb, 1980;McLean and Phillips, 1981;McLean and Phillips, 1982;Slotte and Lundberg, 1983). These values are similar to those found for synthetic phospholipids with 16 -20 effective methylene units (Nichols and Pagano, 1981;McLean and Phillips, 1984;Nichols, 1985).…”

Section: Discussionmentioning

confidence: 67%

Probing Red Cell Membrane Cholesterol Movement with Cyclodextrin

Steck

Lange

2002

Biophysical Journal

234

200

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We probed the kinetics with which cholesterol moves across the human red cell bilayer and exits the membrane using methyl-beta-cyclodextrin as an acceptor. The fractional rate of cholesterol transfer (% s(-1)) was unprecedented, the half-time at 37 degrees C being ~1 s. The kinetics observed under typical conditions were independent of donor concentration and directly proportional to acceptor concentration. The rate of exit of membrane cholesterol fell hyperbolically to zero with increasing dilution. The energy of activation for cholesterol transfer was the same at high and low dilution; namely, 27-28 Kcal/mol. This behavior is not consistent with an exit pathway involving desorption followed by aqueous diffusion to acceptors nor with a simple one-step collision mechanism. Rather, it is that predicted for an activation-collision mechanism in which the reversible partial projection of cholesterol molecules out of the bilayer precedes their collisional capture by cyclodextrin. Because the entire membrane pool was transferred in a single first-order process under all conditions, we infer that the transbilayer diffusion (flip-flop) of cholesterol must have proceeded faster than its exit, i.e., with a half-time of <1 s at 37 degrees C.

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Cholesterol desorption from clusters of phosphatidylcholine and cholesterol in unilamellar vesicle bilayers during lipid transfer or exchange

Cited by 74 publications

References 42 publications

Effect of surface curvature on the rate of cholesterol transfer between lipid vesicles

Effect of surface curvature on the rate of cholesterol transfer between lipid vesicles

Cholesterol transfer between lipid vesicles. Effect of phospholipids and gangliosides

Probing Red Cell Membrane Cholesterol Movement with Cyclodextrin

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