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

Abstract

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.

Properties of phosphatidylcholine in the presence of its monofluorinated analogue

“…Most commonly, with the introduction of compounds that decrease the T m (such as anesthetics and cholesterol) the transition peaks also broaden, as would be expected with the introduction of impurities [36][37][38]. Furthermore, with most lipid mixtures, the transition peak broadens rather than sharpens [18,22,25,26].…”

“…Previous studies have extensively established that mixed lipid systems have the potential to separate into domains [19][20][21][22][23][24][25][26]. The most likely causes for domain formation with DPPC/F-DPPC and DAPC/F-DPPC are thermodynamic phase segregation and hydrophobic mismatch.…”

“…For instance, the fluorine-modified acyl chains can enhance the hydrophobic and lipophobic interactions that control the T m and the solubility of lipophilic probes [11]. Furthermore, these modifications alter membrane fluidity and structure [12], permeability [13], and the behavior of Biophysical Chemistry 147 (2010) [20][21][22][23][24][25][26][27] Abbreviations: DSC, differential scanning calorimeter; T m , main transition temperature; L ′ β , planar gel phase; P ′ β , ripple gel phase; L α , liquid crystalline phase; L β I, interdigitated gel phase, DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine; F-DPPC, 1-palmitoyl-2-[16-fluoropalmitoyl]-sn-glycero-3-phosphocholine; DAPC, 1,2-diarachidoyl-sn-glycero-3-phosphocholine; DPH, 1,6-diphenyl-1,3,5-hexatriene; β-DPH HPC, 2-(3-(diphenylhexatrienyl) propanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine.…”

“…Previous experiments have explored domain formation and phase separation in lipid mixtures involving different chain lengths [19][20][21], headgroups [22], the presence of cholesterol [23], and degrees of unsaturation [24]. In particular, work by Rowe [25] and Mason [26] has shown that it is possible to have coexisting gel and interdigitated phases. Rowe demonstrated that a mixture of dilaurylphosphatidylethanolamine [PE(12:0)/(12:0)] and DPPC underwent lateral phase segregation between the gel phase and the fully-interdigitated phase with the addition of ethanol [25].…”

“…Rowe demonstrated that a mixture of dilaurylphosphatidylethanolamine [PE(12:0)/(12:0)] and DPPC underwent lateral phase segregation between the gel phase and the fully-interdigitated phase with the addition of ethanol [25]. Similarly, Mason found that there could be phase-separated domains of interdigitated and non-interdigitated gel phases with binary combinations of symmetric and mixed-chain phosphatidylcholines [26].…”