Lipid-cholesterol interactions

When the membrane is washed with ether to remove all of the cholesterol, the resultant PMR spectrum shows little change in the intensity of the polymethylene chain signal compared with that of the original membrane spectrum. This appears to rule out lipid-cholesterol interaction in this membrane as having a dominant effect upon the polymethylene chain freedom. In the membrane fragments either lipid chain-chain interactions have increased as a result of the protein interaction... 

Vibrational spectroscopy shows that inclusion of cholesterol in phospholipid bilayers tends to decrease the fluidity of the hydrophobic region above the main transition point Tm and to increase it below Tm. The presence of cholesterol in DPPC or DMPC muti-layered vesicles does not affect the transition point but simply broadens the transition by decreasing the CH2-stretching wavenumber in the liquid crystalline phase and by increasing it in the gel-like phase (Lippert and Peticolas, 1971 Spiker and Levin, 1976 Casal and Mantsch, 1984). There is also evidence that lipid-cholesterol interaction increases the amount of bound water in the headgroups (Levin et al., 1985). 

H. L. Scott, Biophys.]., 59,445 (1991). Lipid-Cholesterol Interactions (Monte Carlo Simulations and Theory). 

Ohvo-Rekila, H., Ramstedt, B., Leppimaki, P. and Slotte, J. P. (2002). Cholesterol interactions with phospholipids in membranes, Progr. Lipid Res., 41, 66-97. 

Lysobisphosphatidic acid (LBPA) also distinguishes late endosomes. LBPA is shaped like an inverted cone it has a much larger head than tail and enters highly curved membrane regions. The lipid may help in the accumulation of molecules like cholesterol by specific lipid-protein interactions (131). 

The spread mixed lipid monolayer studies provide information about the packing and orientation of such molecules at the water interface. These interfacial characteristics affect many other systems. For instance, mixed surfactants are used in froth flotation. The monolayer surface pressure of a pure surfactant is measured after the injection of the second surfactant. From the change in n, the interaction mechanism can be measured. The monolayer method has also been used as a model biological membrane system. In the latter BLM, lipids are found to be mixed with other lipidlike molecules (such as cholesterol). Hence, mixed monolayers of lipids + cholesterol have been found to provide much useful information on BLM. The most important BLM and temperature melting phenomena is the human body temperature regulation. Normal body temperature is 37°C (98°F), at which all BLM function efficiently. 

Discontinuities are seen in the relationship between increase in film pressure, An, and lipid composition following the injection of globulin under monolayers of lecithin-dihydro-ceramide lactoside and lecithin-cholesterol mixtures. The breaks occur at 80 mole % C 16-dihydrocaramide lactoside and 50 mole % cholesterol. Between 0 and 80 mole % lactoside and between 0 and 50 mole % cholesterol the mixed films behave as pure lecithin. Two possible explanations are the formation of complexes, having molar ratios of lecithin-lactoside 1 to 4 and lecithin-cholesterol 1 to 1 and/or the effect of monolayer configurations (surface micelles). In this model, lecithin is at the periphery of the surface micelle and shields the other lipid from interaction with globulin. 

Lipid-Protein Interaction. Although measurements were made over a 40-minute period, for convenience in the presentation of the results (7), only the rise in pressure at 15 minutes is given. A linear relationship was found between film penetration, All, and lipid composition for mixtures of cholesterol and either N-palmitoyl or N-stearoyldihydrosphingosyl lac-toside (Figure 1). 

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... 

There is a long history of controversy in the literature regarding the mode of action of general anesthetics. Experimental results derived from model systems of lipids alone or lipid-cholesterol are somewhat controversial. To mention just a few, using Raman spectroscopy it was found that, at clinical concentrations, halothane had no influence on the hydrocarbon chain conformations, and it was concluded that the interaction between halothane and the lipid bilayer occurs in the head group region [57]. This idea was also supported by 19F-NMR studies. The chemical shifts of halothane in a lipid suspension were similar to those in water and differed from those in hydrocarbons. In contrast, from 2H-NMR experiments, it was concluded that halothane is situated in the hydrocarbon region of the membrane (see also chapter 3.3). 

Vibrational spectroscopy also shows interactions of polyene antibiotic ion channels nystatin and amphotericin B with phospholipid bilayers (Bunow and Lewin, 1977a Iqbal and Weidekamm, 1979 Van de Ven et al., 1984). In particular, Fourier Transform Raman spectroscopy demonstrates that at high temperature, the amphotericin A complex of DPPC/cholesterol is more ordered, whereas the amphotericin B complex is as ordered as the pure lipid/cholesterol system. In the low temperature phase and in the presence of the sterol-antibiotic complex, the bilayers were suggested to be in the interdigitated state (Levin and Neil Lewis, 1990). 

The effect of cholesterol on the thermotropic phase behavior of PC bilayer also varies significantly with the structure, particularly the degree of unsaturation, of the hydrocarbon chains, with more highly unsaturated PCs exhibiting a reduced miscibility with cholesterol and other sterols. Moreover, the structure of the lipid polar headgroup is also important in determining the effect of cholesterol on the host lipid, as is the structure of the sterol molecule itself. For more information on the application of DSC to the biologically important area of lipid-sterol interactions, the reader is referred to recent reviews (23-25). 

Although some membrane proteins are known to interact with cholesterol, cholesterol interactions with other lipids have been studied much more thoroughly. Most notably, cholesterol interacts strongly with sphingomyelin, perhaps by forming complexes, which results in a liquid-liquid phase separation of cholesterol-rich and cholesterol-poor phases (13). The cholesterol-rich phases exhibit more chain order and therefore are referred to as liquid-ordered (lo) phases, whereas the cholesterol-poor phases are called liquid-disordered (Id) phases. 

Lipid—Lipid and Lipid—Protein Interactions. The DPL—cholesterol and the protein—DPL systems are particularly amenable to interpretation using our membrane model. The high viscosity lattice of DPL can be broken by cholesterol (Figure 9), and the lattice of BSA can be broken by a lipid (e.g., DPL, Figure 10), with a marked loss of surface viscosity. This lattice collapse means formation of independent membrane subunits whose lateral valences are saturated within the subunit, thereby producing a fluid system (Figure 1A) the subunit could be a lipid-lipid system, as with DPL and cholesterol, or a lipid-protein system. The phenomenon of lattice collapse with loss of surface viscosity is impressive in the DPL-albumin system since individually both components have a high surface viscosity. 

Cholesterol, which is largely insoluble in aqueous m a, travels through the blood circulation in the form of Upoprotein complexes. The plasma lipoproteins are a family of globular particles that share common structural features. A core of hydrophobic lipid, principally triacylglycerols (triglycerides) and cholesterol esters, is surrounded by a hydrophilic monolayer of phospholipid and protein (the apolipoproteins) [1-3]. Lipid-apolipoprotein interactions, facihtated byi amphi-pathic protein helices that segregate polar from nonpolar surfaces [2,3], provide the mechanism by which cholesterol can circulate in a soluble form. In addition, the apolipoproteins modulate the activities of certain enzymes involved in Upoprotein metabolism and interact with specific cell surface receptors which take up Upopro-teins by receptor-mediated endocytosis. Differences in the Upid and apoUpoprotein compositions of plasma Upoproteins determine their target sites and classification based on buoyant density. 

Net transfer of lipid occurs from the plasma to the erythrocyte membrane, presumably because of a shift in the equihbrium as the plasma lipoproteins become saturated with the excess cholesterol and phosphatidylcholine. This leads to membrane abnormalities and cholesterol-phospholipid ratios of up to 2 1. Changes in cellular physiology of the type referred to in section IV have also been reported [94,96,161]. These must reflect an alteration in lipid-protein interactions within the membranes. The molecular arrangement of the excessive amounts of cholesterol present in the cell membranes in diseased liver cells is not known. In model systems cholesterol is not present in molar amounts greater than 1 1. In liver disease a major change is in cellular morphology with the formation of abnormally shaped erythrocytes, as discussed earlier. 

Ohvo-Rekila H, Ramstedt B, Leppimaki P, Slotte JP. Cholesterol interactions with phospho-hpids in membranes. Prog Lipid Res 41(2002) 66-97. 

Other interfacial chemistries are found in juxtamem-brane domains of certain proteins that show a preferential interaction with specific lipids in their head group region. Important lipids involved in these interactions include the polyphosphate phosphatidylinositol lipids, cholesterol, gangliosides, and sphingomyelin. Interfacial chemistries play a role in the formation of microdomains and can determine the effective concentration of certain amphiphilic drugs in different membranes or even in different leaflets of the same membrane. 

It is a well-known experimental fact that incorporation of cholesterol in lipid bilayers affects the mechanical and transport properties of membranes. This includes their increased bending elasticity (22) and reduced passive permeability to small molecules (23, 24). Despite a great deal of theoretical and experimental research, no definitive microscopic understanding of phospholipid-cholesterol interactions has been proposed yet. 

H. Brockerhoff, Model of Interaction of Polar Lipids, Cholesterol, and Proteins in Biological Membranes, Lipids 9, 645-650 (1974). 

N. Chatteijee and H. Brockerhoff, Evidence for Stereospecific Phospholipid-Cholesterol Interaction in Lipid Bilayers, Biochim. Biophys. Acta 511, 116-119 (1978). 

Table 6 shows that the surface of polycarbonate with adsorbed serum albumin is the most suitable one to be used in implant devices. The behavior of all lipids toward blood-polymer interaction is not similar and may change depending on the nature of lipid, net charge of the lipid-adsorbed surface and the lipid-protein/ lipid-platelet interaction at the interface. Under conditions of high cholesterol concentrations addition of vitamin C leads to suitable surface characteristics of polycarbonate. The question is how to garantee the preferential the albumin adsorption on an implant surface In works of Malmsten and Lassen [123] competitive adsorption at hydrophobic surfaces from binary protein solutions was... 

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