Model membranes cholesterol

Natural biological membranes consist of lipid bilayers, which typically comprise a complex mixture of phospholipids and sterol, along with embedded or surface associated proteins. The sterol cholesterol is an important component of animal cell membranes, which may consist of up to 50 mol% cholesterol. As cholesterol can significantly modify the bilayer physical properties, such as acyl-chain orientational order, model membranes containing cholesterol have been studied extensively. Spectroscopic and diffraction experiments reveal that cholesterol in a lipid-crystalline bilayer increases the orientational order of the lipid acyl-chains without substantially restricting the mobility of the lipid molecules. Cholesterol thickens a liquid-crystalline bilayer and increases the packing density of lipid acyl-chains in the plane of the bilayer in a way that has been referred to as a condensing effect. 

Fig. 11. Evidence that a membrane-associated immunochemical reaction (complement fixation) depends on the mobility of the target hapten (IX) in the plane of a model membrane. The extent of the immunochemical reaction, complement fixation, is measured by A Absorbance at 413 nm. Temperature is always 32°C, which is above the chainmelting temperature (23°C) of dimyristoylphosphatidylcholine used for the data given in A and below the chain-melting transition temperature (42°C) of dipalmitoylphosphatidyl-choline used for the data in B. Thus A refers to a fluid membrane and B refers to a solid membrane. The numbers by each curve are equal to c, the mole % of spin-label hapten IX in the plane of the lipid membrane. It will be seen that complement fixation, as measured by A Absorbance at 413 nm is far more effective in the fluid membrane than in the solid membrane at low hapten concentrations (i.e., c 0.3 mo e%). In C the lipid membrane host is a 50 50 mole ratio mixture of cholesterol and dipalmitoylphosphatidylcholine. The immunochemical data suggest that this membrane is in a state of intermediate fluidity. Specific affinity-purified IgG molecules were used in these experiments. (For further details, see Ref. 5.)... 

Qeveral recent investigations using various physicochemical methods have provided convincing evidence to support the contention that the basic structure of most biological membranes consists of a phospholipid bilayer (1,2,3, 4). Studies on phospholipid model membranes can therefore be expected to yield relevant information on the role played by phospholipids in determining the characteristic properties of biological membranes (5). One important aspect of this problem concerns the mechanisms of interaction between the phospholipids and other membrane constituents such as cholesterol, proteins, and different inorganic... 

The molecular mechanism of local anesthesia, the location of the local anesthetic dibucaine in model membranes, and the interaction of dibucaine with a Na+-channel inactivation gate peptide have been studied in detail by 2H- and 1H-NMR spectroscopy [24]. Model membranes consisted of PC, PS, and PE. Dibucaine was deuterated at H9 and H3 of the butoxy group and at the 3-position of the quinoline ring. 2H-NMR spectra of the multilamellar dispersions of the lipid mixtures were obtained. In addition, spectra of deuterated palmitic acids incorporated into mixtures containing cholesterol were obtained and the order parameter, SCD, for each carbon... 

Ahmed, S.N., Brown, D.A., and London, E. (1997) On the origin of sphingolipid/cholesterol-rich detergent-insoluble cell membranes physiological concentrations of cholesterol and sphingohpid induce formation of a detergent-insoluble, liquid-ordered lipid phase in model membranes. Biochemistry 36 10944-10953. 

Shin, Y. K., and Freed, J. H. (1989), Dynamic imaging of lateral diffusion by electron spin resonance and study of rotational dynamics in model membranes. Effect of cholesterol, Biophys. J., 55, 537-550. 

Pulse field gradient (PFG) NMR spectroscopy is now generally regarded as the method of choice for measuring the translational diffusion coefficients of molecules of virtually any type under many conditions (48). H, H, F, and P variants of this method have been used successfully to study lateral diffusion of cholesterol, phospholipids, and water in model membranes (49,50). This technique introduces two identical gradient pulses of the external magnetic field into the standard spin-echo NMR... 

Crane JM, Tamm LK. Role of cholesterol in the formation and nature of lipid rafts in planar and spherical model membranes. Biophys. J. 2004 86 2965-2979. 

Cheetham, J. J., Hpand, R. M., Andrews, M., and Flanagan, T. D. (1990). Cholesterol sulfate inhibits the fusion of Sendai virus to biological and model membranes. /. BieJ. Cfjcw. 265,12404-12409. 

Lipid rafts on cell membranes are cholesterol- and sphingolipid-rich domains that function as platforms for signal transduction and other cellular processes [6], Tethered lipid bilayers have been proposed as a promising model membrane to describe the structure and function of cell membratKs [7]. Based on these facts, we endeavor to array the lipid rafts as a form of tethered bilayer lipid membrare into the nanopattemed substrates to generate a raft membrane-based biosensing platform (Fig. Ic). 

In this work, we have analyzed the phase behavior of various freeze-dried mixtures of DPPE, DPPC, and cholesterol and have examined the effects of trehalose addition to these liposomes. Generally, dehydration leads to increase in transition temperature of the phospholipids and also to phase separation. Addition of trehalose, however, can prevent the increase in transition temperature and phase separation freeze-dried DPPC-cholesterol liposomes exhibit only one transition and their retention capability increases by more than 40%. Further studies on the phase separation and stability of multicomponent model membranes will be required to understand better its relation to the survival of cells to freeze-drying procedures. 

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