Cholesterol, membrane fluidity

This proves our theory that the membrane fluidity is an important parameter increasing shear stress resistance. The studies give two possibilities of improving the resistance lowering temperature or adding cholesterol. Which one is the most convenient is dependent on the cell line and the constraints of the process. 

The hypothesis that polar carotenoids regulate membrane fluidity of prokaryotes (performing a function similar to cholesterol in eukaryotes) was postulated by Rohmer et al. (1979). Thus, the effects of polar carotenoids on membrane properties should be similar in many ways to the effects caused by cholesterol. These similarities were demonstrated using different EPR spin-labeling approaches in which the effects of dipolar, terminally dihydroxylated carotenoids such as lutein,... 

Recently, due to increased interest in membrane raft domains, extensive attention has been paid to the cholesterol-dependent liquid-ordered phase in the membrane (Subczynski and Kusumi 2003). The pulse EPR spin-labeling DOT method detected two coexisting phases in the DMPC/cholesterol membranes the liquid-ordered and the liquid-disordered domains above the phase-transition temperature (Subczynski et al. 2007b). However, using the same method for DMPC/lutein (zeaxanthin) membranes, only the liquid-ordered-like phase was detected above the phase-transition temperature (Widomska, Wisniewska, and Subczynski, unpublished data). No significant differences were found in the effects of lutein and zeaxanthin on the lateral organization of lipid bilayer membranes. We can conclude that lutein and zeaxanthin—macular xanthophylls that parallel cholesterol in its function as a regulator of both membrane fluidity and hydrophobicity—cannot parallel the ability of cholesterol to induce liquid-ordered-disordered phase separation. 

Cholesterol has a funny effect on membrane fluidity. Because of its shape, cholesterol prevents long-chain fatty acids from packing close to each other. When cholesterol is added to a membrane composed largely... 

MEMBRANE FLUIDITY is regulated by altering the chain length of fatty acids, the presence of m-unsaturations, and the content of cholesterol. 

In the literature, one can find many more interesting MD studies concerning lipid bilayers with additives. In particular, a wealth of MD simulations of such systems is in the field of anaesthetics (for a review see [142]). Many anaesthetics tend to accumulate at the membrane/water interface, implying that their potencies are not related to their ability to cross the membrane. Instead, it seems to be more likely that their functioning is via binding to membrane receptors. Generally, they have an effect opposite to that of cholesterol, i.e. they increase the membrane fluidity and permeability. 

Biological membranes Fluidity and order parameters Determination of the phase transition temperature Effect of additives (e.g. cholesterol)... 

Our laboratory mostly works with PEG-cholesterol. It is easily obtained in one step by addition of cholesteryl chloroformate and amino-methoxy-PEG (31). Introduction of a linker between the cholesterol and the PEG part would induce higher membrane fluidity and reduce more efficiently protein interactions as compared to PEG-cholesterol. A diaminobutane spacer was shown to improve significantly the sustained release of calcein from lipoplexes incubated in 30% serum (32). The spacer effect on bicatenar PEG-lipid has not been intensively studied because it can be expected that it would induce less effect on PEG-dioleoyl than on PEG-cholesterol, the lipidic anchor being predominant in the bilayer stabilization (Fig. 2). 

Cholesterol The pathway for synthesis of cholesterol is described in Appendix 11.9. Cholesterol is important in the structure of membranes since it can occupy the space that is available between the polyunsaturated fatty acids in the phospholipid (Chapter 4). In this position, cholesterol restricts movement of the fatty acids that are components of the phosphoglycerides and hence reduces membrane fluidity. Cholesterol can be synthesised de novo in proliferating cells but it can also be derived from uptake of LDL by the cells, which will depend on the presence of receptors for the relevant apoUpoproteins on the membranes of these cells (Appendix 11.3). 

The fluidity of membranes primarily depends on their lipid composition and on temperature. At a specific transition temperature, membranes pass from a semicrystalline state to a more fluid state. The double bonds in the alkyl chains of unsaturated acyl residues in the membrane lipids disturb the semicrystalline state. The higher the proportion of unsaturated lipids present, therefore, the lower the transition temperature. The cholesterol content also influences membrane fluidity. While cholesterol increases the fluidity of semicrystalline, closely-packed membranes, it stabilizes fluid membranes that contain a high proportion of unsaturated lipids. 

Rog, T., Stimson, L.M., Pasenkiewicz-Gierula, M., Vattulainen, I., Karttunen, M. Replacing the cholesterol hydroxyl group with the ketone group facilitates sterol flip-flop and promotes membrane fluidity. J. Phys. Chem. B 2008, 112, 1946-52. 

Inhibitors of HMG-CoA reductase activity (for example compac-tin240), or compounds that lower the levels of the enzyme (including a number of oxygenated cholesterol derivatives,241- 24 la such as 25-liy-droxycholesterol), not only decrease the formation of polyprenyl diphosphate, but also affect the formation of cholesterol and the polyprenyl side-chains of coenzyme Q. Consequently, prolonged treatment with such compounds may cause side effects, for example, changes in membrane fluidity (see also, Section III,5), decreased activity of membrane enzymes,1214,2,3 and inactivation of membrane transport systems,246 and, therefore, indirectly prevent glvcosvlation of proteins. 

Cholesterol is an important structural component of cellular membranes, where it plays a role in modulating membrane fluidity and phase transitions, and, together with sphingomyelin, forms lipid rafts or caveolae, which are sites where proteins involved in diverse signaling pathways become concentrated. Furthermore, cholesterol is a precursor of oxysterols, steroid hormones, and bile acids. 

A, Inhibition of proteolytic enzymes B, dissociation of hexameric to monomeric form of insulin C, loosening of tight junctions D, increase in membrane fluidity due to cholesterol removal E, reversible ciliostasis F, mucoadhesion and prolonged residence time G, incorporation into lipid bilayer and membrane perturbation H, insulin internalization, increased transcellular transport and I, correlation with CMC. 

Carafoli, E., Santella, L., Branca, D., and Brini, M., 2001, Generation, control, and processing of cellular calcium signals, Crit. Rev. Biochem. Mol. Biol. 36, pp. 107-260 Chalmers, S. and Nicholls, D. G., 2003, The Relationship between Free and Total Calcium Concentrations in the Matrix of Liver and Brain Mitochondria, J. Biol. Chem. 278, p. 19062 Colell, A., Garcia-Ruiz, C., Mari, M., and Fernandez-Checa, J. C., 2004, Mitochondrial permeability transition induced by reactive oxygen species is independent of cholesterol-regulated membrane fluidity, FEBS Lett 560, pp. 63-68... 

Cholesterol - an essential component of mammalian cells - is important for the fluidity of membranes. With a single hydroxy group, cholesterol is only weakly am-phipathic. This can lead to its specific orientation within the phospholipid structure. Its influence on membrane fluidity has been studied most extensively in erythrocytes. It was found that increasing the cholesterol content restricts molecular motion in the hydrophobic portion of the membrane lipid bilayer. As the cholesterol content of membranes changes with age, this may affect drug transport and hence drug treatment. In lipid bilayers, there is an upper limit to the amount of cholesterol that can be taken up. The solubility limit has been determined by X-ray diffraction and is... 

The effects of cholesterol and cholesterol-derived oxysterols on adipocyte ghost membrane fluidity has been studied. It has been found that cholesterol and oxysterols interact differently with rat adipocyte membranes. Cholesterol interacts more with phosphatidylcholine located at the outer lipid bilayer whereas, for example, cholestanone seems to interact more with phospholipids located at the inner layer... 

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