Lipid mixed conformations

Figure 8 (Plate 4). Typical snapshot of DPD simulation results [64]. The hydrophobic part of mixed bilayers of DPPC-like lipids and up to 0.8 mole-fraction of the non-ionic surfactant Ci2E6 (left) and 0.9 (right). The surfactant C]2 chains are represented by grey curves, and the lipid C15 chains are black. The hole in the left conformation is transient on the right they are stable. Reproduced by permission of the Biophysical Society...

Monte Carlo may be used to study the lateral distribution of lipid molecules in mixed bilayers. This of course is a very challenging problem, and, to date, the only way to obtain relevant information for this is to reduce the problem to a very simplistic two-dimensional lattice model. In this case, the lipid molecules occupy a given site and can be in one of the predefined number of different states. These pre-assigned states (usually about 10 are taken), are representative conformations of lipids in the gel or in the liquid state. Each state interacts in its own way with the neighbouring molecules (sitting on neighbouring sites). Typically, one is interested in the lateral phase behaviour near the gel-to-liquid phase transition of the bilayer [69,70]. For some recent simulations of mixtures of DMPC and DSPC, see the work of Sugar [71]. 

This lamellar phase is formed of alternate sheets of lipid and water. The lipidic sheets containing the lecithin and the cholesterol are made of two superposed layers of oriented molecules. Each of these two monolayers is mixed and consists of lecithin and cholesterol molecules arranged side by side with their paraffinic ends turned toward the inside of the sheet and their polar groups (phosphatidyl choline group for lecithin and hydroxyl group for the cholesterol) outward—i.e., toward the adjacent sheet of water. This constitution of each of the two mono-layers forming the lipidic sheet is in conformity with the conclusion arising from the study of mixed monolayers of cholesterol and lecithin spread on the free surface of water (1). 

The lipid has, more or less, the conformation shown in the diagram with all the polar ester groups at one end and the hydrocarbon chains bunched together in a nonpolar region. Oil and water do not mix, it is said, but triglyceride lipids associate with water in a special way. A drop of oil spreads out on water in a very thin layer. It does so because the ester groups sit inside the water and the hydrocarbon side chains stick out of the water and associate with each other. 

Cholesterol is a major hpid component of mammahan cell plasma membranes, accounting for approximately 35% of the total lipid of the membrane. Cholesterol has a chemical structure that is very different from the major polar hpid constiments, which is a consequence of the fused ring system of cholesterol that gives this hpid less conformational flexibihty than the straight chains of the polar lipids. It is thus not surprising that cholesterol does not mix well in membranes and that cholesterol segregates as crystals at around 50-60 mol% in bilayers of several lipids and at a much lower mol fraction of cholesterol in bilayers comprising hpids with unsaturated acyl chains (5). 

Also using IRRAS, Mendelsohn and co-workers have studied monolayers of phospholipids with deuterated acryl chains. In such systems C-H and C-D stretching vibrations can be monitored simultaneously. This permits, for example, observation of individual components in a mixed lipid monolayer or conformational analysis of different parts of the acryl chains. Measurements on mono-layers consisting of tail-end deuterated DPPC molecules showed that the chains posses more conformational order adjacent to the head group than at their tails. ... 

These calculations suggest that /3-casein and egg yolk lecithin do not mix ideally, but the interaction between them promotes a condensation or non-additivity of molecular areas. Also, tt in the egg lecithin—/3-casein system can be as high as 29 dynes/cm (Figure 4) whereas the maximum pressure exerted by the protein alone is about 22 dynes/cm (Figure 2). Of course, the assumption that the interfacial conformation of the protein is unchanged by the presence of lipid is valid only when is less than the collapse pressure of the pure protein film. Between this point and 29 dynes/cm the protein has probably only partially penetrated. Further information about the nature of the lipid-protein interaction can be gained from the data in Figure 4. 

The picture is fairly clear for the sharply altered behavior of 5-NS, 5-NS (Me), and the rest of the series in view of the ready stabilza-tion of the bent conformation, it is less clear for the differences between other positions of the oxazolidine ring on the chain. In particular, a detailed evaluation of changes in the role that a bent conformation might play for 12-NS and 16-NS requires further study of mixed lipid films. While it seems likely that under typical membrane conditions a bent conformation will play only a minor role, present indications are that it is not negligible and will vary with the shift from the 12 to the 16 position (24). 

---