N-succinyldioleoylphosphatidylethanolamine: structural preferences in pure and mixed model membranes.
The structural preferences of the pH-sensitive phospholipid, N-succinyldioleoylphosphatidylethanolamine (N-succinyl-DOPE), have been examined alone and in mixtures with DOPE by 31P-NMR, fluorescence energy transfer, and freeze-fracture techniques. The basic polymorphic behavior of pure N-succinyl-DOPE and DOPE/N-succinyl-DOPE lipid systems and the influence of calcium and pH were investigated. It is shown that, similar to other negatively charged acidic phospholipids, N-succinyl-DOPE adopts the bilayer organization upon hydration. This structure is maintained at both pH 7.4 and 4.0 in the presence or absence of calcium. In the mixed lipid system, N-succinyl-DOPE can stabilize the non-bilayer lipid, DOPE, into a bilayer structure at both pH 7.4 and 4.0 at more than 10 mol% N-succinyl-DOPE, although a narrow 31P-NMR lineshape is observed at acidic pH values. This corresponds to the presence of smaller vesicles as shown by quasi-elastic light scattering measurements. Addition of equimolar calcium (with respect to N-succinyl-DOPE) to the DOPE/N-succinyl-DOPE systems induces the hexagonal HII phase at both pH values. In unilamellar systems with similar lipid composition the addition of Ca2+ results in membrane fusion as indicated by fluorescence energy-transfer experiments. These findings are discussed with regard to the molecular mechanism of the bilayer to hexagonal HII phase transition and membrane fusion and the utility of N-succinyl-DOPE containing pH-sensitive vesicles as drug-delivery vehicles.
Nayar
R
R
Department of Cell Biology, University of Texas M.D. Anderson Hospital and Tumor Institute at Houston 77030.
Tilcock
C P
CP
Hope
M J
MJ
Cullis
P R
PR
Schroit
A J
AJ
D002118:Calcium / Q000494:pharmacology; D005614:Freeze Fracturing; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008854:Microscopy, Electron; D010714:Phosphatidylethanolamines
D008051:Lipid Bilayers; D008567:Membranes, Artificial; D010714:Phosphatidylethanolamines; C047813:N-succinyl-1,2-dioleoylphosphatidylethanolamine; D002118:Calcium