Polymorphic phase behavior of cardiolipin derivatives studied by 31P NMR and X-ray diffraction

The polymorphic phase behavior of cardiolipin (diphosphatidylglycerol) analogues with two to five chains per phospholipid head group, namely, dilysocardiolipin, monolysocardiolipin, cardiolipin, and acylcardiolipin, respectively, has been studied by 31P NMR and X-ray diffraction. Dilysocardiolipin dispersions at low salt concentration are micellar, and a transition to a lamellar phase takes place between 1 and 2 M NaCl. From light-scattering measurements, it is also found that a transition takes place from the micellar state with a midpoint at 5.2 mM CaCl2, 0.95 M HClO4, and 1.5 M NaCl. Monolysocardiolipin dispersions are lamellar throughout the concentration range from zero to saturated NaCl. Cardiolipin dispersions undergo a transition from a lamellar to an inverted hexagonal phase between 1 and 2 M NaCl. Acylcardiolipin dispersions are in an inverted hexagonal phase throughout the concentration range from zero to saturated NaCl. The chemical shift anisotropies of both phosphate groups in dilysocardiolipin and of one of the phosphate groups in monolysocardiolipin are drastically reduced in the lamellar phase, indicating a different conformation of the phosphatidyl head group from that normally found in diacyl phospholipid bilayers. The results provide strong support for the "shape" concept of lipid polymorphism when viewed in its most general form including configurational entropy, hydrophobic effects, etc. and indicate the importance of head-group interactions in determining the lipid phase behavior.