Sterols in membranes: structural features that rule the interaction with phospholipids

WENZ J.J.

Sierra de la Ventana

Congreso; XLIII Reunión anual de la Sociedad Argentina de Biofísica; 2014

Sociedad Argentina de Biofísica

The relationship between sterol structure and the effects on membrane properties is still controversial. This study introduces a multivariate analysis that relates the molecular structure with the activity of sterols on phospholipid bilayers. Chemical structures were encoded by using binary variables reporting on the presence/absence of substituents in the pentaneperhydrophenanthrene. The sterol activity was encoded regarding physical properties affected in sterol-containing membranes. By means of Principal Coordinates Analysis, the sterol population was grouped into five well-defined clusters according to structural similarities/differences. An examination of the sterol distribution between clusters revealed that a hydroxyl group at C3 and an 8-10 carbon chain at C17 are common in sterols having rigidifying, molecular ordering/condensing effects and/or a raft promoting ability. In contrast, sterol containing a keto group at C3, a C4-C5-double bond, and polar groups or a short alkyl side-chain at C17 (3 to 7 atoms) are mostly present in sterols having opposite effects. Combined with Logistic Regression, these approaches conclude that the most important structural features affecting the physical properties of sterol-containing mixtures were the presence of an 8-10 carbon C17 isoalkyl side-chain, followed by a hydroxyl group at C3 and a C5-C6 double bond. Finally, a simple structure-based Logistic Regression model that predicts the activity of sterols is proposed.