Sterol Chemical Structure and Conformation Influence the Thermotropic Phase Behaviour of Dipalmitoylphosphatidylcholine Bilayers

Abstract

Studying the nature of interactions between the sterol ring system and neigbouring phospholipid molecules is important for our understanding of the properties of sterols in biological molecules and the role of such interactions in many disease processes. In this project, the thermotropic phase behaviour of binary dipalmitoylphosphatidylcholine (DPPC)/sterol mixtures with different sterol ring configurations (C5,6 double bond, 5α-H and 5β-H orientation and either 3α-OH, 3β-OH, 3-ketone functional groups) was investigated using differential scanning calorimetry (DSC) and was compared to earlier studies of cholesterol/ and epicholesterol/DPPC mixtures. Given the differences in the thermodynamic parameters obtained from these mixtures and their associated changes in bilayer stability and miscibility, it is clear that changing the sterol chemical configuration has a significant effect on bilayer properties. Any sterol molecule whose ring structure deviates from that of cholesterol is unlikely to be fully miscible in mammalian membranes.