Biological membranes contain a mixture of phospholipids with varying degrees of hydrocarbon chain unsaturation. Mixtures of long chain saturated and unsaturated lipids with cholesterol have attracted a lot of attention because of the formation of two coexisting fluid bilayer phases in such systems over a broad range of temperature and composition. Interpretation of the phase behavior of such ternary mixtures must be based on a thorough understanding of the phase behavior of the binary mixtures formed with the same components. This article describes the phase behavior of mixtures of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) with 1,2-di-d(31)-palmitoyl-sn-glycero-3-phosphocholine (DPPC) between -20 and 50 degrees C. Particular attention has been paid to the phase coexistence below about 16 degrees C where the subgel phase appears. The changes in the shape of the spectrum (and its spectral moments) during the slow transformation process leads to the conclusion that below 16 degrees C the gel phase is metastable and the gel component of the two-phase mixture slowly transforms to the subgel phase with a slightly different composition. This results in a line of three-phase coexistence near 16 degrees C. Analysis of the transformation of the metastable gel domains into the subgel phase using the nucleation and growth model shows that the subgel domain growth is a two dimensional process.

The distribution of ionizable amino lipids (KC2) is critical in structure of lipid nanoparticles, siRNA entrapment and endosomal release. Neutral KC2 segregates from phospholipids (POPC) and forms an oily core in the bilayer interior.

Static (2)H NMR spectroscopy is used to study the critical behavior of mixtures of 1,2-dioleoyl-phosphatidylcholine/1,2-dipalmitoyl-phosphatidylcholine (DPPC)/cholesterol in molar proportion 37.5:37.5:25 using either chain perdeuterated DPPC-d62 or chain methyl deuterated DPPC-d6. The temperature dependence of the first moment of the (2)H spectrum of the sample made with DPPC-d62 and of the quadrupolar splittings of the chain-methyl-labeled DPPC-d6 sample are directly related to the temperature dependence of the critical order parameter η, which scales as [Formula: see text] near the critical temperature. Analysis of the data reveals that for the chain perdeuterated sample, the value of Tc is 301.51 ± 0.1 K, and that of the critical exponent, βc = 0.391 ± 0.02. The line shape analysis of the methyl labeled (d6) sample gives Tc = 303.74 ± 0.07 K and βc = 0.338 ± 0.009. These values obtained for βc are in good agreement with the predictions of a three-dimensional Ising model. The difference in critical temperature between the two samples having nominally the same molar composition arises because of the lowering of the phase transition temperature that occurs due to the perdeuteration of the DPPC.

Inverted/reverse hexagonal (H II ) phases are of special interest in several fields of research, including nanomedicine. We used molecular dynamics (MD) simulation to study H II systems composed of dioleoylphosphatidylethanolamine (DOPE) and palmitoyloleoylphosphatidylethanolamine (POPE) at several hydration levels and temperatures. The effect of the hydration level on several H II structural parameters, including deuterium order parameters, was investigated. We further used MD simulations to estimate the maximum hydrations of DOPE and POPE H II lattices at several given temperatures. Finally, the effect of acyl chain unsaturation degree on the H II structure was studied via comparing the DOPE with POPE H II systems. In addition to MD simulations, we used deuterium nuclear magnetic resonance ( 2 H NMR) and small-angle X-ray scattering (SAXS) experiments to measure the DOPE acyl chain order parameters, lattice plane distances, and the water core radius in H II phase DOPE samples at several temperatures in the presence of excess water. Structural parameters calculated from MD simulations are in excellent agreement with the experimental data. Dehydration decreases the radius of the water core. An increase in hydration level slightly increased the deuterium order parameter of lipids acyl chains, whereas an increase in temperature decreased it. Lipid cylinders undulated along the cylinder axis as a function of hydration level. The maximum hydration levels of PE H II phases at different temperatures were successfully predicted by MD simulations based on a single experimental measurement for the lattice plane distance in the presence of excess water. An increase in temperature decreases the maximum hydration and consequently the radius of the water core and lattice plane distances. Finally, DOPE formed H II structures with a higher curvature compared to POPE, as expected. We propose a general protocol for constructing computational H II systems that correspond to the experimental systems. This protocol could be used to study H II systems composed of molecules other than the PE systems used here and to improve and validate force field parameters by using the target data in the H II phase.