colfosceril-palmitate and 1-2-linoleoylphosphatidylcholine

The lipid mixture of DPPC (saturated lipid)/DUPC (unsaturated lipid)/CHOL (cholesterol) is studied with respect to its ability to form liquid-ordered and liquid-disordered phases. We employ coarse-grained simulations with MARTINI force field. All three components are systematically modified in order to explore the relevant molecular properties, leading to phase separation. Specifically, we show that the DPPC/DUPC/CHOL system unmixes due to enthalpic DPPC-DPPC and DPPC-CHOL interactions. The phase separation remains unchanged, except for the formation of a gel phase at long times after decreasing the conformational degrees of freedom of the unsaturated DUPC. In contrast, the phase separation can be suppressed by softening the DPPC chains. In an attempt to mimic the ordering and unmixing effect of CHOL the latter is replaced by a stiff and shortened DPPC-like lipid. One still observes phase separation, suggesting that it is mainly the rigid and planar structure of CHOL which is important for raft formation. Addition of an extra bead to the head of CHOL has no notable impact on the phase separation of the system, supporting the irrelevance of the Umbrella model for the phase separation. Reduction of the conformational entropy of CHOL by stiffening its last bead results in a significant increase of the order of the DPPC/CHOL domain. This suggests that the conformational entropy of CHOL is important to prohibit the gelation process. The interleaflet interactions as mediated by the terminal molecular groups seem to have a strong impact on the possibility of a subsequent gelation process after phase separation.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Cholesterol; Entropy; Lipid Bilayers; Membrane Lipids; Membrane Microdomains; Models, Chemical; Molecular Conformation; Molecular Dynamics Simulation; Phosphatidylcholines

For the biophysical study of membranes, a variety of model systems have been used to measure the different parameters and to extract general principles concerning processes that may occur in cellular membranes. However, there are very few reports in which the results obtained with the different models have been compared. In this investigation, we quantitatively compared the phase coexistence in Langmuir monolayers, freestanding bilayers and supported films composed of a lipid mixture of DLPC and DPPC. Two-phase segregation was observed in most of the systems for a wide range of lipid proportions using fluorescence microscopy. The lipid composition of the coexisting phases was determined and the distribution coefficient of the fluorescent probe in each phase was quantified, in order to explore their thermodynamic properties. The comparison between systems was carried out at 30mN/m, since it is accepted that at this or higher lateral pressures, the mean molecular area in bilayers is equivalent to that observed in monolayers. Our study showed that while Langmuir monolayers and giant unilamellar vesicles had a similar phase behavior, supported films showed a different composition of the phases with the distribution coefficient of the fluorescent probe being close to unity. Our results suggest that, in supported membranes, the presence of the rigid substrate may have led to a stiffening of the liquid-expanded phase due to a loss in the degrees of freedom of the lipids as a consequence of the proximity of the solid material.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Cell Membrane; Fluorescent Dyes; Lipid Bilayers; Lipids; Models, Biological; Phosphatidylcholines; Thermodynamics

Ternary mixtures of saturated and unsaturated phospholipids and cholesterol constitute a well-known model system to study raft formation in membranes. This phenomenon is, e.g., observed in cell membranes. Here, coarse-grained (CG) and microscopic united-atom (UA) simulations are performed to investigate the phase separation of a membrane bilayer for the ternary system of saturated 16:0 (DPPC) and unsaturated 18:2 (DUPC) phospholipids and cholesterol (CHOL). The results of a 9 μs UA simulation demonstrate the onset of phase separation and can be compared with properties of the corresponding CG system. While sharing the structural features of phase separation in the CG model, the onset of demixing for the UA model is 40 times slower. This factor can be rationalized by the different short-time diffusion constants. Various system properties such as order parameters and lipid-CHOL and CHOL-CHOL interactions are analyzed and compared between the UA and CG models. From the structural perspective, the phase separation process appears to be rather similar for both models, which illustrates once more the power of using CG approaches.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Cholesterol; Computer Simulation; Diffusion; Kinetics; Lipid Bilayers; Models, Molecular; Phosphatidylcholines; Temperature; Thermodynamics