Interaction of cholesterol with synthetic sphingomyelin derivatives in mixed monolayers

To study the structural requirements of the molecular interactions between cholesterol and sphingomyelins in model membranes, sphingomyelin derivatives were synthesized in which (a) the 3-hydroxy group was replaced with a hydrogen atom or with a methoxy, ethoxy, or tetrahydropyranyloxy group, (b) the N-acyl chain length was varied, and (c) the N-acyl chain length contained an alpha-hydroxy group. The chemical syntheses of these derivatives from DL-erythro-sphingosine are reported. The properties of these sphingomyelin derivatives were examined in monolayer membranes at the air/water interface. The mean molecular area of the pure N-stearoylsphingomyelin derivatives was determined, and the effects of cholesterol on the condensation of sphingomyelin packing in the monolayer were recorded. It was observed that replacement of the 3-hydroxy group of sphingomyelin with a hydrogen atom or its substitution with a methoxy or ethoxy group did not affect the ability of cholesterol to condense the molecular packing in monolayers. Even when a bulky tetrahydropyranyloxy group was introduced at the 3-hydroxy position of egg sphingomyelin, cholesterol was still able to condense the molecular packing of this derivative. The condensing effect of cholesterol on derivatives of N-stearoyl-SPMs was significantly larger than the comparable effect observed with 1,2-distearoyl-sn-glycero-3-phosphocholine or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine. Our results with 3-hydroxysphingomyelins having differing N-acyl chain lengths (i.e., N-stearoyl, N-myristoyl, and N-lauroyl), and with 3-hydroxy-N-(alpha-hydroxypalmitoyl)sphingomyelin also indicated that cholesterol was able to induce condensation of the molecular packing.(ABSTRACT TRUNCATED AT 250 WORDS)