Cation-dependent segregation phenomena and phase behavior in model membrane systems containing phosphatidylserine: influence of cholesterol and acyl chain composition.

The addition of Ca2+ to model membrane systems containing phosphatidylserine (PS) can have remarkable effects on the distribution of PS and the overall polymorphic phase [bilayer or hexagonal (HII)] assumed by the lipid mixture. In this study, we examine the influence of Ca2+ on lipid mixtures composed of well-defined (synthetic) species of PS, phosphatidylethanolamine (PE), and phosphatidylcholine (PC) in the presence and absence of cholesterol by employing 31P and 2H NMR, freeze-fracture, and X-ray techniques. It is shown that whereas Ca2+ can segregate PS into crystalline cochleate domains in equimolar mixtures of dioleoyl-PE and dioleoyl-PS (DOPS), such effects are not observed for mixtures containing more unsaturated (dilinoleoyl) species of PS. The addition of cholesterol to these PE-PS systems inhibits Ca2+-induced segregation of DOPS and facilitates Ca2+-triggered hexagonal (HII) phase formation for both the PE and the PS components. In contrast, in equimolar mixtures of DOPS with dioleoyl-PC, Ca2+-induced segregation of phospholipid is not affected by the presence of up to 33 mol % cholesterol. These and related effects suggest that, in multicomponent biomembrane systems containing both PE and cholesterol, phase segregation of PS by Ca2+ may not be readily achievable. These results are discussed with regard to the reliability of 31P NMR phase identifications of phospholipid structure in model and biological membranes and demonstrate that in mixed lipid systems the influence of divalent cations on lipid distribution and structure can be exquisitely sensitive to details of the local lipid composition.(ABSTRACT TRUNCATED AT 250 WORDS)