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 C20 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 leads to liquid crystalline phase transition of dipalmitoylphosphatidylcholine (DPPC) and of dielaidoylphosphatidylethanolamine (DEPE) monitored by differential scanning calorimetry and (2) The effect on the lamellar leads to hexagonal HII phase transition of DEPE monitored by DSC and by 31P-NMR to determine structural changes. The gel leads to 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 delta H values becomes 7.1 kcal X mol-1 as compared to 8.2 kcal X mol-1 for the pure lipid. 22,S-OH cholesterol has a much stronger effect (delta H = 3.1 kcal X mol-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 degrees C in the presence of 20,S-OH cholesterol). The delta H 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 lamellar leads to hexagonal HII 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 delta H of the transition was not strongly affected. The molecular interfacial 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 3 beta- and 22,R-positions orients with the sterol nucleus lying flat at the air/water interface, since the compression isotherm of either the pure sterol or the DOPC-sterol mixture (molar ratio, 1:1) monomolecular film exhibits a transition at approx. 103 A2.(ABSTRACT TRUNCATED AT 400 WORDS)