Surface Properties and Membrane Packing in Hybrid Liposomes Composed of Tetraether and Diester Lipids

Archaeal bipolar tetraether lipids are extraordinarily stable against biochemical and physical stressors and non-toxic to animals; thus, they are appealing biomaterials that hold great promise for technological applications. Here, we used electrophoretic mobility measurements and TNS fluorescence to determine zeta potential and surface potential of liposomes (∼150 nm in diameter) composed of archaeal tetraether lipids and conventional diester lipids. We also used Laurdan fluorescence to explore membrane packing in the same membrane system. The polar lipid fraction E (PLFE) from the archaeon S. acidocaldarius was used as the tetraether component. PLFE lipids are asymmetric macrocyclic molecules carrying a negative charge on the phosphate moiety at one of the two polar ends at neutral pH. We found that zeta potential varies with PLFE content in a biphasic manner, being most negative when the PLFE content is ∼60 mol%. Surface potential is also PLFE content dependent, showing a minimum at ∼50 mol% PLFE. On the other hand, Laurdan GP (generalized polarization) data, inferentially membrane packing, displays a peculiar behavior at 20-40 mol% PLFE. In a separate study, we used the AAPH-induced Laurdan fluorescence intensity change to deduce information about membrane packing. AAPH (2,2'-azobis (2-amidinopropane) dihydrochloride) is a water-soluble, free-radical generator. Upon addition of AAPH, there was a lag time (t), followed by a steady decrease in Laurdan fluorescence intensity due to probe oxidation. The t values as well as the initial rate (R) of AAPH-induced Laurdan oxidation were found to change with PLFE mole fraction in a non-monotonic manner, showing an anomaly between 20-50 mol % PLFE. These data together suggest that, in the range 20-50 mol %, these hybrid liposomes undergo major structural changes engendered by PLFE content.