Interactions Determining Stereoselectivity in Two-Dimensional Systems─The Case of 22-Hydroxycholesterol Epimers.

Abstract

Oxidized derivatives of cholesterol play an important role in the functioning of biomembranes. Unlike other biomolecules, which are physiologically active in only one enantiomeric form, some oxysterols exist endogenously as two stereoisomers that exhibit strictly different biological effects. In this paper, we focused our attention on 22-hydroxycholesterol (22-OH) epimers, 22(R)-OH and 22(S)-OH, and examined their properties in Langmuir monolayers spread at the air/water interface, using classical surface manometry complemented with Brewster angle microscopy (BAM) images of the film texture. The studied epimers showed quite different monolayer characteristics. Namely, 22(S)-OH formed homogeneous, condensed monolayers of high collapse pressure, while 22(R)-OH films were more disordered and expanded with quite low collapse pressure. Interestingly, the latter compound showed in the course of the surface pressure-molecular area isotherm a temperature-dependent plateau transition, characterized by the coexistence of domains of molecules with different inclinations, visible in BAM images as patches of varying brightness. Molecular dynamics (MD) simulations confirmed this and revealed that the greater structural variability of 22(R)-OH is due to the greater hydration of the oxygen atom at C(22) compared to the other epimer. Next, we tested whether 22-OH epimers could differentiate interactions with sphingomyelin (SM). Although the strength of interaction with SM was similar for both epimers, the composition of the films corresponding to this minimum was different. With the aid of MD, it was found that these differences result directly from the interplay between 22-OH molecules and their ability for hydrogen bond formation. Therefore, the stereochemistry of oxysterols seems to play a crucial role in the overall structural organization of the membrane.