Lipid dynamics, cholesterol effects

Robinson, A. J., Richards, W. G., Thomas, P. J. and Hann, M. M. (1995). Behavior of cholesterol and its effect on head group and chain conformations in lipid bilayers a molecular dynamics study, Biophys. J., 68, 164-170. 

Figure 4 Effect on the serum stability of the incorporation of 5% cholesterol poly(ethy-lene glycol) (PEG) into cationic lipoplexes [hpopolyamine RPR209120/DOPE1/1, ratio (mol) lipid/DNA = 10 in 150 mM NaCl]. Lipoplexes were incubated in DMEM + 10% SVF, at 37°C, aliquots were regularly sampled and monitored by dynamic diffusion. Results represent a mean between three measurements. Error bars are not presented to simplify the graph, but differences among PEG, PEG-1, and PEG-2 are significant. Abbreviations PEG, poly(ethylene glycol) DOPE, dioleylphosphatidylethanolamine DMEM, Dulbecco s Modified Eagle Medium.

Kucerka, N., Perlmutter, J.D., Pan, J., Tristram-Nagle, S., Katsaras, J., Sachs, J.N. The effect of cholesterol on short- and long-chain monounsaturated lipid bilayers as determined by molecular dynamics simulations and X-ray scattering. Biophys. J. 2008, 95, 2792-805. 

In the previous two sections we discussed the electrodeformation and electroporation of vesicles made of single-component membranes in water. In this section, we consider the effect of salt present in the solutions. The membrane response discussed above was based on data accumulated for vesicles made of phosphatidylcholines (PCs), the most abundant fraction of lipids in mammahan cells. PC membranes are neutral and predominantly located in the outer leaflet of the plasma membrane. The inner leaflet, as well as the bilayer of bacterial membranes, is rich in charged lipids. This raises the question as to whether the presence of such charged lipids would influence the vesicle behavior in electric fields. Cholesterol is also present at a large fraction in mammalian cell membranes. It is extensively involved in the dynamics and stability of raft-hke domains in membranes [120]. In this section, apart from considering the response of vesicles in salt solutions, we describe aspects of the vesicle behavior of fluid-phase vesicles when two types of membrane inclusions are introduced, namely cholesterol and charged lipids. 

It has recently been shown that introduction of a small, hydrophobic molecule like isoprene may lead to a more ordered and better packed lipid membrane as revealed by MD simulations. The stabilized membrane is then protected against temperature-induced disordering of the tails. Similar thermoprotective effects are induced by cholesterol which also increases the molecular packing of the tails and, in contrast to isoprene, affects the dynamics of the lipids in the bilayer. ... 

The aim of the present study was to investigate the shortterm effects of DAG especially on the dynamics of postprandial serum lipids (8). A postprandial increase in remnant lipoproteins was also examined after oral loading of different types of oil emulsions, which contained either DAG or TAG of the same fatty acid composition, in a randomized, double-blind, crossover design. For the detection of changes in remnant lipoproteins after oral fat loading, we used measurements of cholesterol (RLP-C) and triacylglycerol (RLP-TG) in remnant-like lipoprotein particles (RLP) in the serum (9-11). 

The technique was beautifully illustrated in a recent combined 250 GHz and 9 GHz study on membrane vesicles composed of pure lipid (DPPC) and of DPPC with cholesterol in a 1 1 molar ratio using the end-chain labelled lipid 16-PC. Using sophisticated computer modelling it was shown that the 250 GHz spectra were only sensitive to rapid internal dynamics of the end chain whereas the 9 GHz spectra were also sensitive to the overall motion of the lipid and the primary effect of the cholesterol was to restrict the range of motion whilst simultaneously allowing faster motion of the end-chain dynamics. 

Incorporation of cholesterol into model membranes increase the order parameter of the hydrocarbon chains but leaves the lipid lateral diffusion almost unaffected (12). Therefore it can be concluded that the effect of cholesterol on the packing properties of the bilayers is more important than its influence on lipid bilayer dynamics. 

Biomembranes are complex structures composed of various lipids and proteins. Different membrane compositions affect viscoelastic and hydrodynamic properties of membranes, which are critical to their functions. Cholesterol-rich vesicles are similar to cell membranes in structure and component. Therefore, cholesterol-rich vesicles can represent a typical model for studying membrane dynamics and functions. Nuclear magnetic relaxation dispersion was used to investigate the detailed molecular dynamics of membrane differences between vesicles and cholesterol vesicles in the temperature range of 278-298 K. Vesicles of two different sizes were prepared. The effect of cholesterol mainly affected the order fluctuation of membranes and the diffusional motion of lipid molecules. ... 

It is clear from a variety of spectroscopic techniques that biomembranes are dynamic not static structures. It is also known that certain membrane functions depend critically on the fluidity of the membrane lipids. Spin-labelled and fluorescent-labelled lipid probes are found to perform rotational motions in the nanosecond timescale in fluid lipid bilayers and membranes. For diffusive rotation the characteristic correlation times are given by the Debye equation (t = n V/kT) and correspond to effective viscosities in the range q 0.1-1 poise. A spin-labelled steroid analogue of cholesterol for instance rotates rapidly about its long... 

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