Bilayer fluidity

The use of Upid bilayers as a relevant model of biological membranes has provided important information on the structure and function of cell membranes. To utilize the function of cell membrane components for practical applications, a stabilization of Upid bilayers is imperative, because free-standing bilayer lipid membranes (BLMs) typically survive for minutes to hours and are very sensitive to vibration and mechanical shocks [156,157]. The following concept introduces S-layer proteins as supporting structures for BLMs (Fig. 15c) with largely retained physical features (e.g., thickness of the bilayer, fluidity). Electrophysical and spectroscopical studies have been performed to assess the appUcation potential of S-layer-supported lipid membranes. The S-layer protein used in aU studies on planar BLMs was isolated fromB. coagulans E38/vl. 

Direct observation of molecular diffusion is the most powerful approach to evaluate the bilayer fluidity and molecular diffusivity. Recent advances in optics and CCD devices enable us to detect and track the diffusive motion of a single molecule with an optical microscope. Usually, a fluorescent dye, gold nanoparticle, or fluorescent microsphere is used to label the target molecule in order to visualize it in the microscope [31-33]. By tracking the diffusive motion of the labeled-molecule in an artificial lipid bilayer, random Brownian motion was clearly observed (Figure 13.3) [31]. As already mentioned, the artificial lipid bilayer can be treated as a two-dimensional fluid. Thus, an analysis for a two-dimensional random walk can be applied. Each trajectory observed on the microscope is then numerically analyzed by a simple relationship between the displacement, r, and time interval, T,... 

Major determinants of membrane fluidity may be grouped within two categories [53] (1) intrinsic determinants, i.e., those quantifying the membrane composition and phase behavior, and (2) extrinsic determinants, i.e., environmental factors (Table 1). In general, any manipulation that induces an increase in the molal volume of the lipids, e.g., increase in temperature or increase in the fraction of unsaturated acyl chains, will lead to an increase in membrane fluidity. In addition, several intrinsic and extrinsic factors presented in Table 1 determine the temperature at which the lipid molecules undergo a transition from the gel state to liquid crystalline state, a transition associated with a large increase in bilayer fluidity. 

Vesicle size, bilayer fluidity, membrane permeability, microviscosity, ability to bind small molecules, suseeptibility to pore formation, flip-flop rates, extent of water penetration, lateral amphiphile diffusion, vesiele fusion, and kinetic medium effeets (some of which will be discussed briefly below) all depend on the paeking of... 

Similarly, vesicular reactivity is dependent on bilayer fluidity and Arrhenius (or Eyring) plots for the decarboxylation of 6-NBIC show a break around Tm. " For the Kemp elimination in different bilayers, it was found that the bilayer for which kinetic data had been gathered below its was least effective as a catalyst. Ester hydrolysis has also been found to be faster above r. For the decarboxylation of 6-NBIC, the increase in catalytic efficiency was attributed to different aggregate surface dynamics based on the observation that vesicles above showed intermediate activation parameters between vesicles below and micelles. One could, of course, discuss causality here considering the fact that many of the bilayer... 

Grammer et al. [120] studied collagen shield with dissolution times of 12 h, that were presoaked with either hydrophilic or lipophilic fluorophore (4,5-carboxyfluorescein and jV-[Lissamine rhodamine B sulfonyl]-diacyl-phosphatidylethanolamine, respectively), in a solution or unilamellar liposome suspension with different surface charges and bilayer fluidity. For the hydrophilic fluorophore, two to seven times higher concentrations were achieved in the collagen shield by immersion in aqueous solution than immersion in the liposome suspensions. 

The release kinetics data results indicated that liposome surface charge and bilayer fluidity are of minor importance for the interaction of liposomes with collagen shields. Moreover, the release kinetics of hydrophilic or lipophilic substance from collagen shield was similar for both liposome-encapsulated and nonencapsulated drug. Thus, these results suggest that there is no added value for combined application of collagen shields and liposomes. In another study, the combination of collagen shield and liposomes enhanced CsA ocular penetration but failed to provide sustained release compared to CsA liposomal suspension [121]. 

Cholesterol has also been employed as a colipid due to its ability to modify bilayer fluidity. Inclusion of cholesterol results in the formation of more stable but less efficient in vitro complexes than those containing DOPE. In contrast, addition of cholesterol results in very active complexes for in vivo administration [123— 127]. 

Kirjavainen, M., Monkkonen, J., Saukkosaari, M. etal. Phospholipids affect stratum corneum lipid bilayer fluidity and drug partitioning into the bilayers. J. Control. Release 1999 58 207-14. 

Beastall, J., Hadgraft, J. and Washington, C. (1988). Mechanism of action of Azone as a percutaneous penetration enhancer Lipid bilayer fluidity and transition temperature effects. Int. J. Pharm. 45 207-213. 

CH has well-known effects on lipid bilayer rigidity and stability (17). Bilayer stability effects are reflected by the effect of CH concentration on phase transition temperature (18), saturated lipid segregation, bilayer fusion temperature and bilayer fluidity (19). 

In a subsequent study, van Hal et al. [40] reported that a decrease in cholesterol content in liquid state bilayers, which increases bilayer fluidity, resulted in an increase in estradiol transport across SC. With confocal laser scanning microscopy, Meuwissen et al. examined the diffusion depth of gel- vs. liquid-state liposomes labeled with fluorescein-dipalmitoylphosphatidylethanolamine (fluorescein-DPPE) with human skin in vitro [41] (Figure 3) and rat skin in vivo [42] and found that the lipophilic label when applied in liquid-state bilayers onto the skin penetrated deeper into the skin than when applied in gel-state liposomes. Recently, Fresta and Puglisi [43] reported that corticosteroid dermal delivery with skin-lipid liposomes was more effective than delivery with phospholipid vesicles, both with respect to higher drug concentrations in deeper skin layers and therapeutic effectiveness. This is a very surprising result, because skin lipid liposomes are rigid and form stacks of lamellae on the surface of the skin [44]. From the previously mentioned studies it seems clear that the thermodynamic state of the bilayer plays a crucial role in the effect of vesicles on dmg transport rate across skin in vitro. 

Gordon, L. M., Sauerheber, R. D., Esgate, J. A., Dipple, I., Marchmont, R. J., and Houslay, M. D., The increase in bilayer fluidity of rat liver plasma membranes achieved by the local anesthetic benzyl alcohol affects the activity of intrinsic membrane enzymes, /. Biol. Chem., 255, 4519, 1980. 

Catalysis of 6-nitrobenzisoxazole-3-carboxylate (NBOC) decarboxylation by N,N dimethyl dialkylam-monium bromide vesicles is modulated by the bilayer fluidity [40], Catalytic efficiency increases with temperature, but at the phase transition there is a sharp increase in the catalysis. Several parameters, such as substrate binding constants, extent of ion dissociation and reactivity of NBOC, may change simultaneously at the Tc, com-... 

Lyles, D. S., and Landsberger, F. R., 1977, Sendai virus-induced hemolysis Reduction in heterogeneity of erythrocyte lipid bilayer fluidity, Proc. Natl. Acad. Sci. USA 74 1918. 

The effect of bilayer fluidity on the immimogenicity of membrane-soluble antigens showed that liposomes made of phospholipids with a higher than ambient temperature (37°C) (solid liposomes) [129,130] provoked strong... 

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