Mixing behavior of symmetric chain length and mixed chain length phosphatidylcholines in two-component multilamellar bilayers: evidence for gel and liquid-crystalline phase immiscibility.

The mixing behavior of symmetric chain length and mixed chain length phosphatidylcholines in two-component multilamellar bilayers has been investigated by high-sensitivity differential scanning calorimetry. Phase diagrams have been constructed for two-component bilayers composed of C(18)C(18)PC and either C(18)C(16)PC, C(18)C(14)PC, C(18)C(12)PC, or C(18)C(10)PC. It is found that C(18)C(18)PC-C(18)C(16)PC and C(18)C(18)PC-C(18)C(14)PC mixed bilayers exhibit complete miscibility of the components in both the gel and liquid-crystalline phases. Whereas this mixing is observed to be nearly ideal for the C(18)C(18)PC-C(18)C(16)PC binary system, the intermixing of the lipids is highly nonideal in the gel phase of the C(18)C(18)PC-C(18)C(14)PC binary mixture. The C(18)C(18)PC-C(18)C(12)PC and C(18)C(18)PC-C(18)C(10)PC mixed bilayers are characterized by partial immiscibility of the phosphatidylcholine components in the bilayer gel phase. Over a large compositional range, these bilayers appear to consist of phase-separated regions of interdigitated and noninterdigitated gel phases. In addition, the C(18)C(18)PC-C(18)C(10)PC two-component bilayer displays a limited region of liquid-liquid immiscibility in the liquid-crystalline bilayer phase. The phase separation of the mixed chain length phosphatidylcholines revealed in these mixed bilayers may represent a three-dimensional phase separation of the lipid components where the phosphatidylcholines are both laterally separated within the plane of the bilayer and conformationally coupled across the bilayer. Such phase-separated domains could have profound effects on membrane structure and function if they were to occur in biological membranes.