Effects of Low Concentrations of Docosahexaenoic Acid on the Structure and Phase Behavior of Model Lipid Membranes

In this paper we report an X-ray diffraction study on the phase behavior of binary lipid mixtures of 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine (DHA-PE) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) at low concentrations below 5.0 mol% DHA-PE. Our results show that DHA-PE induces phase separation into a DHA rich liquid crystalline (L(α)) phase and a DHA poor gel (L(β′)) phase at overall DHA-PE concentrations as low as 0.1 mol%. In addition, we find that the structure of the L(β′) phase, from which the DHA-PE molecules are largely excluded, is modified in the phase-separated state at low DHA-PE concentrations, with a decrease in bilayer thickness of 1.34 nm for 0.1 mol% at room temperature, compared to pure DPPC bilayers. This result is contrary to that seen in similar studies on mono-unsaturated lipids where an increase in bilayer thickness is observed. The surprising effect of such low DHA-PE concentrations on membrane structure may be important in understanding the role of highly polyunsaturated lipids in biological membrane-based structures and similar artificial surfactant systems.