Bilayer stability

Veiga, M.P., Arrondon, J.L. Goni, P.M. and Alonso, A., 1999, Ceramides in phospholipid membranes effects on bilayer stability and transition to nonlamellar phases. Biophys. 7. 76 342-350... 

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). 

The ability of compounds 21, 22, 23, 25, and 28-32 to conduct cations was examined in planar bilayers composed of phosphatidylethanolamine (PE) painted across a 200 pm diameter aperture in a septum between two aqueous compartments filled with 600 mM KC1 (10 mM HEPES pH 7.2) (Figure 13). Bilayer quiescence was confirmed at 148 mV and bilayer stability was observed to be unaffected by the addition of up to 5 pL of DMSO. Stock solutions of the channel compounds (10 pM) were prepared immediately prior to use, and 0.1-5 pL (i.e. 1-50 pmol of substance) in DMSO was added to the stirred solution in the cis chamber. Typically, channel insertion into the bilayer occurred between 30 s and 30 min. 

Fig. 3.82 represents schematically the generally accepted molecular model of such bilayer. The description of the fluctuation formation of microscopically small holes responsible for the bilayer stability and permeability can be based on both thermodynamic and molecular models. First some thermodynamic results will be outlined and then the results obtained with the aid of model considerations. 

The application of an external electric field across a bilayer may also affect the bilayer stability for otherwise-stable BLMs, for example, it is known [e.g. 425,426] that an electric field can drastically shorten their lifetime. This effect arises from a decrease in the work involved in hole formation due to the application of the field. If W l is the work involved in the formation of an /-sized hole in the presence of an externally applied electric field of voltage V it has been found [e.g. 426] that... 

Dependence of the lifetime of foam bilayers on the concentration of dissolved surfactant. The stability of foam, emulsion and membrane bilayers can be characterised by their mean lifetime r which is the time elapsing form the moment of formation of a bilayer with a given radius until the moment of its rupture. Obviously, this is a kinetic characteristic of the bilayer stability and can only be applied to thermodynamically metastable bilayers. 

Muller et. al. [421] have studied the behaviour of emulsion Newton bilayer films and compared it to that of foam films. They determined the dependence of the lifetime on surfactant concentration of emulsion films stabilised with 22-oxythylated dodecyl alcohol (see Section 3.4.1). Experimental data for both kinds of films proved to be in conformity with the theory of bilayer stability (see Section 3.4). The values of the equilibrium concentrations Ce calculated for emulsion films were higher (Ce 10 3 mol dm 3) than those for foam films (Ce 3 1 O 5 mol dm 3). It is worth noting that Ce value of foam films from certain surfactants is lower than CMC (C < CMC) while for emulsion films - Ce > CMC. That is why it is impossible to obtain thermodynamically stable films in the latter case. This result is of particular importance for the estimation of stability of aqueous emulsions with bilayer films between the drops of the organic liquid. 

In order to apply the hole-nucleation theory of bilayer stability of Kashchiev-Exerowa [27] involving quantitative interpretation of the W(C) dependence (probability for observation of black films vs. surfactant concentration), the black films from amniotic fluid should be bilayer films. This is proved experimentally by two dependences Y hw) (Fig. 11.1) and hw(Cei) (Fig. 11.2). As it can be seen in Fig. 11.1, the equivalent film thickness is 8 nm and does not change with the increase in IT (which is the difference between the pressures in the... 

The above mentioned threshold dilution d, and critical concentration for formation of a bilayer are used as measures for bilayer stability [19] being determined by the first neighbour lateral and normal interactions in the foam bilayer. This is the difference of the parameter d, from the change in the free surface energy which is usually used as a measure of the surface activity. Thus, the parameters d, and C, are proposed as new characteristics of the surface activity of an amphiphile molecule, evaluated with high accuracy from the sharp W(d) and W(C) dependences, respectively. 

Let us summarise the conditions of formation of a microscopic foam film in order to serve the in vivo situation. These are film radius r from 100 to 400 pm capillary pressure pa = 0.3 - 2.5-102 Pa electrolyte (NaCl) concentration Ce 0.1 mol dm 3, ensuring formation of black films (see Section 3.4) and close to the physiological electrolyte concentration sufficient time for surfactant adsorption at both film surfaces. Under such conditions it is possible also to study the suitable dependences for foam films and to use parameters related to formation and stability of black foam films, including bilayer films (see Section 3.4.4). For example, the threshold concentration C, is a very important parameter to characterise stability and is based on the hole-nucleation theory of bilayer stability of Kashchiev-Exerowa. As discussed in Section 3.4.4, the main reason for the stability of amphiphile bilayers are the short-range interactions between the first neighbour molecules in lateral and normal direction with respect to the film plane. The binding energy Q of a lipid molecule in the foam bilayer has been estimated in Section 11.2. 

The SLB is conventionally formed on silica surfaces and stabilized by interactions between the hydrophilic hydroxyl surface and the phospholipid headgroups. It is purely a phospholipid bilayer stabilized only by electrostatics and the hydrophobic... 

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). 

For the example application of a loaded polymersome, we require Xnab 30.5. The determination of the coefficients of the hydrophilic moieties is motivated by reproducing for them good solvent conditions. In the following, we set all the third order virial coefficients between the hydrophilic units to zero. The second order coefficients should have a positive value, which in the case of the B monomers determines the size of the hydrophilic head of the amphiphile. The coefficient vbb has to be empirically determined to comply with the bilayer stability (e.g., large values of vbb gives rise to micelle formation instead of bilayers). In this work, we use vbb = vqc = 0.1. Substitution of vbb and into (17) yields vMi = -6. Table 1 summarizes the values of the virial coefficients used to study the loaded polymer-somes. 

Cholesteryl-cyclodextrins Cholesteryl-CyDs have been designed, and are obtained by grafting a cholesterol group onto a CyD. Indeed, cholesterol is described as a phospholipid-bilayer stabilizer and the cholesterol part of cholesteryl-CyDs can enter this bilayer whereas CyD, the hydrophilic part, is located in the internal and external aqueous media between bilayers [90, 91]. 

The release of active compounds from liposomes is directly related to liposomal bilayer stability. Therefore, a controlled-release profile from CyD-containing liposomes is difficult to obtain because of interaction between inclusion complexes and the hpidic vesicle (cholesterol and phospholipids) [103]. Indeed, lipid/CyD complex formation can occur within the hposomes, thus destabilizing the liposomal bilayer [85]. Liposome destabilization is also closely related to the stability of the encapsulated complex the higher the affinity between drug and CyD, the slower the drug release [84]. 

In mammals, phallotoxins, and certainly also virotoxins, are absorbed from the intestines into the blood only slowly, if at all (in contrast to the amatoxins). After intraperitoneal injection they rapidly reach the liver and exert their similar toxic effect there. They weaken the structure of the hepatocyte membrane, hence blood penetrates the Uver cells and the periphery is depleted of blood to such an extent that anemic shock occurs from internal bleeding. A cause of damage to the membranes is supposedly the very strong binding of phallotoxins and virotoxins to F-actin that under the lipid-bilayer stabilizes the membrane. At this point a brief discussion of actin is necessary. 

Nanoscaled particles with a disk-shaped lipid bilayer stabilized by an apolipo-protein scaffold (curcumin nanodisks, NDs, with <50 nm size) have been used for encapsulating curcumin. NDs self-assemble in solution upon presentation of the scaffold protein to a phospholipid vesicle substrate to which an appropriate hydro-phobic bioactive agent has been introduced. The incorporation of curcumin into NDs enhanced growth inhibition of human hepatocellular carcinoma cells (HepG2) and induced apoptosis in mantle cell lymphoma (Jeko cells) [115,116]. Natthakittaet al. reported the development of mucoadhesive curcumin nanospheres. Ethyl cellulose... 

J Weaver and R Mintzer, Decreased bilayer stability due to trans-... 

The calculations were in agreement with the experimental results. Therefore, stable magnetic fluids with positively charged magnetite particles and with bilayer stabilized magnetite particles could be prepared. 

Jo is the strength of the van der Waals interactions. Ca,% and Cc,% are occupation variables of lipid molecules (in the various chain states) and cholesterol molecules. The interaction strengths are given by the shape-dependent nematic parameters and Ic [4]. n is an internal pressure to assure bilayer stability. 

Positively charged CTAB bilayer stabilizes the nanorods... 

Holland, J. W., Madden, T., and Cullis, P., 1996, Bilayer stabilizing components and their use in forming programmable fusogenic liposomes. PCT WO 96/10392. 

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