Lipid tails

Scheme 27. Noncovalent functionalization of SWNTs by using an amphiphilic glycopolymer, ending with a lipid tail for mucin mimicry.249...

Liposomes are artificial structures primarily composed of phospholipid bilayers exhibiting amphiphilic properties. Other molecules, such as cholesterol or fatty acids also may be included in the bilayer construction. In complex liposome morphologies, concentric spheres or sheets of lipid bilayers are usually separated by aqueous regions that are sequestered or compartmentalized from the surrounding solution. The phospholipid constituents of liposomes consist of hydrophobic lipid tails connected to a head constructed of various glycerylphosphate... 

Figure 2. This figure gives a schematic illustration of various fluctuations that exist in lipid bilayers. From top to bottom (1) the increase in area and concomitant reduction in membrane thickness is strongly damped. (2) Up and down movements of the lipids are restricted to small amplitudes, i.e. much less than the tail length. (3) Interpenetration of lipids into the opposite monolayer is, in first approximation, forbidden. (4) Conformations of the lipid tails have only few gauche defects, so that the tail is only slightly curved. Reproduced from (58) with permission from the Biophysical Society...

From these overall profiles, it is not easy to extract conformational properties, other than that it will be clear that the lipid molecules are strongly anisotropically oriented in the bilayer. For this, other characteristics are much more appropriate. It is possible to define an order parameter which indicates how much the lipid tails are oriented normal to the membrane ... 

With respect to SCF models that focus on the tail properties only (typically densely packed layers of end-grafted chains), the molecularly realistic SCF model exemplified in this review needs many interaction parameters. These parameters are necessary to obtain colloid-chemically stable free-floating bilayers. A historical note of interest is that it was only after the first SCF results [92] showed that it was not necessary to graft the lipid tails to a plane, that MD simulations with head-and-tail properties were performed. In the early MD simulations (i.e. before 1983) the chains were grafted (by a spring) to a plane it was believed that without the grafting constraints the molecules would diffuse away and the membrane would disintegrate. Of course, the MD simulations that include the full head-and-tails problem feature many more interactions than the early ones. 

Figure 13. The overall density (volume fraction) profile for DMPC bilayers is shown here. Apart from the distribution of the overall DMPC molecules, the density distribution of the head-group units (including the choline group, the phosphate group and the oxygens of the glycerol unit), and the end groups of the lipid tails are also indicated. In addition, the free-volume profile and the water profile are depicted...

From the modelling results for bilayers composed of unsaturated lipids one can begin to speculate about the various roles unsaturated lipids play in biomembranes. One very well-known effect is that unsaturated bonds suppress the gel-to-liquid phase transition temperature. Unsaturated lipids also modulate the lateral mobility of molecules in the membrane matrix. The results discussed above suggest that in biomembranes the average interpenetration depth of lipid tails into opposite monolayers can be tuned by using unsaturated lipids. Rabinovich and co-workers have shown that the end-to-end distance of multiple unsaturated acyl chains was significantly less sensitive to the temperature than that of saturated acyls. They suggested from this that unsaturated... 

Prenylation of proteins (a posttranslational modification) that need to be held in the cell membrane by a lipid tail. An example is the p21 G protein in the insulin and growth factor pathways. 

We have also undertaken MD simulations to examine the effect of cholesterol content on the thermodynamics of DPPC desorption [54], We found that DPPC had a lower affinity for bilayers with high cholesterol content (Figure 3B). This suggests that while cholesterol prefers to interact with saturated lipid tails, the saturated tails might not prefer to interact with cholesterol. It would be interesting to repeat this study on unsaturated lipid tails. 

V is the volume of the alkyl chain (depends on the fluidity of the lipid tail and therefore on the temperature). 

Fig. 1. Lipid substitution patterns for the polymerization of lipid bilayers, featuring polymerization of the lipid tails at (A) the chain terminus, (B) near the lipid backbone or polymerization of reactive groups (C) covalently or (D) electrostatically associated with the hydrophilic headgroup.

Figure 7 Plot of the change in the product of the coupling and maximum saturation factors as a function of macromolecular structure. At lower pH values, the spin-labelled lipids are present as vesicles and vesicular aggregates, while at higher pH values, micelles are formed. The higher psmax values for the micelles imply greater water accessibility to the radical site. The solid circles represent 16-DS (16-doxyl stearic acid, spin-labelled at the end of the lipid tail) while the open circles represent 5-DS (5-doxyl stearic acid, spin-labelled near the polar head group). Reproduced with permission from Ref. [70].

Daptomycin might not have been developed if Lilly did not have a group working on enzymatic bioconversions. Without this capability, the deacylase enzyme from A. utahensis10 would not have been discovered and so the chemical SAR studies around the lipid tail leading to daptomycin might not have been approachable. 

Basically, the lateral force originates from the deformation of the bilayer in the presence of a protein with a hydrophobic region of different thickness than the bilayer. An example in which the hydrophobic region of the protein is too long for the bilayer tails is illustrated in Fig. 6. (Similar arguments apply if the protein is too short for the lipid tails.)... 

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