The Structure of Oxysterols Determines Their Behavior at Phase Boundaries: Implications for Model Membranes and Structure-Activity Relationships

The presence of an additional polar group in the cholesterol backbone increases the hydrophilicity of resulting compounds (oxysterols), determines their arrangement at the phase boundary, and interactions with other lipids and proteins. As a result, physicochemical properties of biomembranes (i.e., elasticity, permeability, and ability to bind proteins) are modified, which in turn may affect their functioning. The observed effect depends on the type of oxysterol and its concentration and can be both positive (e.g., antiviral activity) or negative (disturbance of cholesterol homeostasis, signal transduction, and protein segregation). The membrane activity of oxysterols has been successfully studied using membrane models (vesicles, monolayers, and solid supported films). Membrane models, in contrast to the natural systems, provide the possibility to selectively examine the specific aspect of biomolecule-membrane interactions. Moreover, the gradual increase in the complexity of the used model allows to understand the molecular phenomena occurring at the membrane level. The interest in research on artificial membranes has increased significantly in recent years, mainly due to the development of modern and sophisticated physicochemical methods (static and dynamic) in both the micro- and nanoscale, which are applied with the assistance of powerful theoretical calculations. This review provides an overview of the most important findings on this topic in the current literature.