Lipid aggregation

Further addition of fatty acid eventually results in the formation of micelles. Micelles formed from an amphipathic lipid in water position the hydrophobic tails in the center of the lipid aggregation with the polar head groups facing outward. Amphipathic molecules that form micelles are characterized by a unique critical micelle concentration, or CMC. Below the CMC, individual lipid molecules predominate. Nearly all the lipid added above the CMC, however, spontaneously forms micelles. Micelles are the preferred form of aggregation in water for detergents and soaps. Some typical CMC values are listed in Figure 9.3. 

Figure 13.5 (a) Fluorescence micrograph of the self-spreading lipid bilayer doped with a dye molecule. The lipid bilayer spread on an oxidized silicon wafer from a deposited lipid aggregate illustrated on the left, (b) A schematic drawing of the selfspreading lipid bilayer from the lipid aggregate. Adapted from Ref [48] with permission. 

Routine use of in-line filters with TNA solutions is controversial. A 1.2-micrometer filter can be used to prevent catheter occlusion caused by precipitates or lipid aggregates, and to remove Candida albicans. 

Despite the fact that many different cationic lipids have been synthesized and tested for transfection (25 34), relatively few systematic structure activity TE-relationship studies have been performed (35 39). As a result, no general relationship between chemical structure and TE could be drawn from these studies. One reason for this is that the chemical structure of a cationic lipid is not directly responsible for TE. TE rather depends on the biophysical characteristics of the cationic lipid aggregate (e.g., liposomes and lipoplexes), which, for its part, is dependent on the chemical structure of the lipids. In a previous study with analogs of the transfection lipid A-[l-(2,3-dioleoyloxy) propyl]-A,A,A-trimethylammoniumchloride (DOTAP) (40) which differ in their nonpolar hydrocarbon chains, it could be shown that the TE strongly depended on the biophysical properties of the resulting liposomes and lipoplexes (35). Minimal alterations of biophysical properties by using lipids with different hydrocarbon chains or by mixing the lipid with different neutral helper lipids could completely allow or prevent transfection. 

Depending on the precise conditions and the nature of the lipids, three types of lipid aggregates can form when amphipathic lipids are mixed with water (Fig. 11-4). Micelles are spherical structures that contain anywhere from a few dozen to a few thousand amphipathic molecules. These molecules are arranged with... 

FIGURE 11-4 Amphipathic lipid aggregates that form in water, (a) In... 

Glycerophospholipids, as well as other lipids, aggregate and align to form a bilayer (Figure 3.18). Both faces of the bilayer are polar because of the orientation of the polar... 

When temperature is raised, the membrane bilayer not only becomes increasingly fluid due to enhanced motions of acyl chain, but it also tends to shift increasingly towards forming lipid aggregates in the inverted hexagonal phase (.hexagonal II, Hn, phase) (Hazel, 1995). The temperature at which this type of phase change... 

Certain spectroscopic techniques, such as nuclear magnetic resonance (NMR) methods, require that the membrane mimetic, i.e., the lipid aggregate is not too large, and that the lipids exhibit a high degree of motion. For such studies, the micellar membrane model is often preferred. Micelles are relatively small (Fig. 3, top), which means that they rotate rapidly, on the time-scale required for NMR. These micelles consist of detergent molecules that aggregate above the critical micelle concentration (CMC). The size of a micelle is defined by the... 

First, the question of where nucleotide monomers may have come from is critical. Given that the formose reaction is the most likely candidate for the synthesis of prebiotic ribose, but yields very little pure material, the role of stereoselective catalysts (clays, amino acids, or lipid aggregates) in directing the reaction should be fully explored. In this respect, Wachters-hauser16 has advanced a scheme for nucleotide synthesis based on pyrite catalysis than can be readily tested. 

Unlike simulations of proteins and protein complexes, modeling and simulations of lipid systems is relatively easy in the sense that lipid molecules and (smallest) lipid aggregates are reasonably small, and the time scales related to many processes that take place in lipid systems are of the order of nanoseconds. Consequently, even atomistic modeling of lipid aggregates is feasible for reasonably complex systems. Here, we discuss briefly the three main levels of modeling associated with lipids. 

It is of interest to note here that the behaviour of lipid aggregates for which the optimal shape is a spherical vesicle or an infinite bilayer will be quite different from that of rod-shaped micelles. One might anticipate by analogy with rods that finite disc-like bilayers could form with cylindrical rims. For such a system the free energy would take the form = n +akT/N. From section 2, for large a, the system will assemble spontaneously into infinite bilayers. Repetition of an analysis similar to that for rods leads to values of a sufficiently large so that this process always occurs. 

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