Influence of cholesterol on the structural preferences of dioleoylphosphatidylethanolamine-dioleoylphosphatidylcholine systems: a phosphorus-31 and deuterium nuclear magnetic resonance study

Abstract

The polymorphic phase behavior of mixtures of synthetic dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC) and the influence of cholesterol on these phase preferences were investigated by NMR techniques. In particular, 31P NMR procedures are used to study the overall phase preferences of these mixed systems, whereas 2H NMR is employed to monitor the structural preferences of individual components of these systems by using DOPE and DOPC which are 2H labeled at the C11 position of the acyl chains. DOPE-DOPC systems containing as little as 20 mol % DOPC initially assume lamellar structure at 40.degree. C, even though DOPE in isolation prefers the hexagonal (HII) organization at this temperature. However, this lamellar organization appears to represent a metastable state, as incubation for extended periods at 40.degree. C results in formation of a structure, possibly the cubic phase, in which the phospholipids experience isotropic motional averaging. The addition of cholesterol induces hexagonal (HII) phase organization. 2H NMR studies of appropriately labeled versions of these systems indicate that cholesterol does not produce such effects by associating preferentially with either DOPE or DOPC. Further, in situations where bilayer, hexagonal or isotropic phases coexist in the same sample, the phospholipids exhibit apparently ideal mixing behavior.