Sterol-phospholipid interactions in model membranes Effect of polar group substitutions in the cholesterol side-chain at C20 and C22

Abstract

The interactions of phospholipids with four different cholesterol derivatives substituted with one OH or one keto group at position C2o or C22 of the side-chain were studied. The derivatives were the 22,R-hydroxy; 22,S-hydroxy; 22-keto-and 20,S-hydroxycholesterol. Two aspects of the interactions were investigated: (1) the effect of the cholesterol derivatives on the gel--, liquid crystalline phase transition of dipalmitoylphosphatidylcholine (DPPC) and of dielaidoyiphosphatidylethanolamine (DEPE) monitored by differential scanning calorimetry and (2) The effect on the lamellar--, hexagonal H n phase transition of DEPE monitored by DSC and by 3t P-NMR to determine structural changes. The gel ---, liquid crystalline phase transition was affected by the cholesterol derivatives to a much larger extent in the case of DPPC than of DEPE. In both cases, there was a differential effect of the four derivatives, the 22,R-hydroxycholesterol being the less effective. In DPPC-sterol 1 : 1 systems, 22,R-hydroxycholesterol does not suppress the melting transition, the AH values becomes 7.1 kcal. mol-1 as compared to 8.2 kcal. mol-1 for the pure lipid. 22,S-OH cholesterol has a much stronger effect (AH = 3.1 kcai. tool-1) and 22-ketocholesterol suppresses the transition completely. In DEPE mixtures of all these compounds, the melting transition of the phospholipid is still observable. The transition temperature was shifted to lower values (-13.5°C in the presence of 20,S-OH cholesterol). The AH of the transition was lowered by these compounds except in DEPE-22,R-OH cholesterol mixtures and the cooperativity of the transition (reflected by the width at half peak height) was reduced. The lameilar --, hexagonal H t~ phase transition was also affected by the presence of these cholesterol derivatives. The transition temperature value was depressed with all these compounds. 20,S-OH cholesterol was the most effective followed by 22,R-OH cholesterol. The AH of the transition was not strongly affected. The molecular intedacial properties of these derivatives were studied by the monomolecular film technique. It is most likely that 22,R-OH cholesterol due to the hydroxyl groups at the * To whom correspondence should be sent at (present address): E.R. No. 64 du Centre National de la Recherche Scientifique, Unit~ d'Enseignements et de Recherche Biom~dicale des Saints-P~res, 45, rue des Saints-P~res, 75270 Paris C~dex 06, France. Abbreviations: DEPE, 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine; DOPE, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine; DOPC, 1,2-dioleoyl-sn-glycero-3-phosphocholine; EDTA, ethylenediaminetetraacetic acid; 22,R-OH cholesterol, (22,22,(22,20, 22-ketocholesterol, 5-cholestene-3fl-ol-22-one; cytochrome P-450sc¢, cytochrome P-450 specific for the side-chain cleavage of cholesterol.0005-2736/84/$03.00 © 1984 Elsevier Science Publishers B.V. 973~-and 22,R-positions orients with the sterol nucleus lying flat at the air/water interface, since the compression isotherm...

Fluorocholesterols, in contrast to hydroxycholesterols, exhibit interfacial properties similar to cholesterol

“…This contrasts with 22,S-OHCH or 20,S-OHCH, which appear to orient vertically at large molecular areas (39). In our work, the slight rises in surface pressures between 140 and 200 Å 2 /molecule from 0.7 and 1.2 mN/m to 1.1 and 2.2 mN/m for 27OHCH and 25OHCH, respectively, compared to the sharp rise with 22,R-OHCH (39), are consistent with the entire side chain of these terminally hydroxylated sterols lying horizontal at the interface. In this configuration, the side chain will undergo cis-trans conformational isomerizations and alter its length.…”

“…5) suggests that like the dihydroxy bile acids (21), 25OHCH and 27OHCH are oriented horizontally at the interface at large molecular areas (Ͼ140 Å 2 ), with the 3-OH and the side chain OH anchored to the interface. Also based on surface balance experiments, the horizontal orientation of 22,R-OHCH, another side chain OHCH, has been suggested, because of a lift-off at 103 Å 2 /molecule (39). This contrasts with 22,S-OHCH or 20,S-OHCH, which appear to orient vertically at large molecular areas (39).…”

“…Also based on surface balance experiments, the horizontal orientation of 22,R-OHCH, another side chain OHCH, has been suggested, because of a lift-off at 103 Å 2 /molecule (39). This contrasts with 22,S-OHCH or 20,S-OHCH, which appear to orient vertically at large molecular areas (39). In our work, the slight rises in surface pressures between 140 and 200 Å 2 /molecule from 0.7 and 1.2 mN/m to 1.1 and 2.2 mN/m for 27OHCH and 25OHCH, respectively, compared to the sharp rise with 22,R-OHCH (39), are consistent with the entire side chain of these terminally hydroxylated sterols lying horizontal at the interface.…”

Fluorescence of .DELTA.5,7,9(11),22-ergostatetraen-3.beta.-ol in micelles, sterol carrier protein complexes, and plasma membranes

“…Fluorescence anisotropy, differential scanning calorimetry, and 31P NMR demonstrated that oxidized derivatives of cholesterol did not suppress the melting phase transition of phospholipid liposomes as did pure cholesterol (Vincent & Gallay, 1983;Gallay et al, 1984). Oxidized sterols did not bind to the same site on oxysterol carrier protein as cholesterol (Kandutsch & Shown, 1981).…”

Versatile ginsenoside Rg3 liposomes inhibit tumor metastasis by capturing circulating tumor cells and destroying metastatic niches

“…By analyzing the structure of ginsenoside Rg3, we found that its steroid ring structure, side chain of C17, and hydroxyl of C3 site satisfy all conditions proposed by researchers that required for liposome membrane regulators (fig. S1) ( 19 ), which means that Rg3 has the potential as a stabilizer by inserting into the liposome membrane and interacting with phospholipids. The glucose moieties in the hydrophilic part of Rg3 will theoretically extend out of the liposome surface, which is the perfect ligand for glucose transporter 1 (Glut1) overexpressed in TNBC ( 20 ), implying that Rg3 may have the ability to target and capture CTCs after inserted into liposomes.…”