Lipid bilayers applications

Jorgensen, K., Ipsen, J. H., Mouritsen, O. G., Bennett, D. and Zuckermann, M. J. (1991). The effects of density fluctuations on the partitioning of foreign molecules into lipid bilayers application to anaesthetics and insecticides, Biochim. Biophys. Acta, 1067, 241-253. 

E. A. Haigh, K. R. Thulborn, and W. H. Sawyer, Comparison of fluorescence energy transfer and quenching methods to establish the position and orientation of components within the transverse plane of the lipid bilayer. Application to the gramicidin A-bilayer interaction, Biochemistry 18, 3525-3532 (1979). 

Altenbach C, Greenhalgh DA, Khorana HG, Hubbell WL. A collision gradient-method to determine the immersion depth of nitrox-ides in lipid bilayers. Application to spin-labeled mutants of bac-teriorhodopsin. Proc. Natl. Acad. Sci. U.S.A. 1994 91 1667-1671. Fanucci GE, Cafiso DS. Recent advances and applications of site-directed spin labeling. Curr. Opin. Struct. Biol. 2006 16 644-653. 

The development of monoalkyl phosphate as a low skin irritating anionic surfactant is accented in a review with 30 references on monoalkyl phosphate salts, including surface-active properties, cutaneous effects, and applications to paste and liquid-type skin cleansers, and also phosphorylation reactions from the viewpoint of industrial production [26]. Amine salts of acrylate ester polymers, which are physiologically acceptable and useful as surfactants, are prepared by transesterification of alkyl acrylate polymers with 4-morpholinethanol or the alkanolamines and fatty alcohols or alkoxylated alkylphenols, and neutralizing with carboxylic or phosphoric acid. The polymer salt was used as an emulsifying agent for oils and waxes [70]. Preparation of pharmaceutical liposomes with surfactants derived from phosphoric acid is described in [279]. Lipid bilayer vesicles comprise an anionic or zwitterionic surfactant which when dispersed in H20 at a temperature above the phase transition temperature is in a micellar phase and a second lipid which is a single-chain fatty acid, fatty acid ester, or fatty alcohol which is in an emulsion phase, and cholesterol or a derivative. 

A review is given of the application of Molecular Dynamics (MD) computer simulation to complex molecular systems. Three topics are treated in particular the computation of free energy from simulations, applied to the prediction of the binding constant of an inhibitor to the enzyme dihydrofolate reductase the use of MD simulations in structural refinements based on two-dimensional high-resolution nuclear magnetic resonance data, applied to the lac repressor headpiece the simulation of a hydrated lipid bilayer in atomic detail. The latter shows a rather diffuse structure of the hydrophilic head group layer with considerable local compensation of charge density. 

The lipid molecule is the main constituent of biological cell membranes. In aqueous solutions amphiphilic lipid molecules form self-assembled structures such as bilayer vesicles, inverse hexagonal and multi-lamellar patterns, and so on. Among these lipid assemblies, construction of the lipid bilayer on a solid substrate has long attracted much attention due to the many possibilities it presents for scientific and practical applications [4]. Use of an artificial lipid bilayer often gives insight into important aspects ofbiological cell membranes [5-7]. The wealth of functionality of this artificial structure is the result of its own chemical and physical properties, for example, two-dimensional fluidity, bio-compatibility, elasticity, and rich chemical composition. 

Here the basic concepts and the method for strictly determining DD sites in lipid bilayer membranes are viewed, together with some examples of their applications. 

The method utilizing ID NMR is simple and eonvenient. Henee the NMR method diseussed here ean be applied to the systematie investigation of the membrane irug inter-aetions, elosely related to the vital function in biomembranes. It is expected that the application can be extended to the lipid-peptide interaction and protein uptake. We are now applying the method to apolipoprotein binding with lipid bilayers and emulsions. Preferential protein binding sites in membranes can be specified by NMR on the molecular level. 

Amphipathic peptides contain amino acid sequences that allow them to adopt membrane active conformations [219]. Usually amphipathic peptides contain a sequence with both hydrophobic amino acids (e.g., isoleucine, valine) and hydrophilic amino acids (e.g., glutamic acid, aspartic acid). These sequences allow the peptide to interact with lipid bilayer. Depending on the peptide sequence these peptides may form a-helix or j6-sheet conformation [219]. They may also interact with different parts of the bilayer. Importantly, these interactions result in a leaky lipid bilayer and, therefore, these features are quite interesting for drug delivery application. Obviously, many of these peptides are toxic due to their strong membrane interactions. 

All of the above-mentioned examples describe organosiloxane hybrid sheet-like structures. However, cell-mimicry requires spherical structures that can form an inner space as a container. Liposomes and lipid bilayer vesicles are known as models of a spherical cell membrane, which is a direct mimic of a unicellular membrane. However, the limited mechanical stability of conventional lipid vesicles is often disadvantageous for some kinds of practical application. 

Activation of PE residues with these crosslinkers can proceed by one of two routes the purified PE phospholipid may be modified in organic solvent prior to incorporation into a liposome, or an intact liposome containing PE may be activated while suspended in aqueous solution. Most often, the PE derivative is prepared before the liposome is constructed. In this way, a stable, stock preparation of modified PE may be made and used in a number of different liposomal recipes to determine the best formulation for the intended application. However, it may be desirable to modify PE after formation of the liposomal structures to ensure that only the outer half of the lipid bilayer is altered. This may be particularly important if substances to be entrapped within the liposome are sensitive or react with the PE derivatives. 

Chiu, S. W., Clark, M. M., Jakobsson, E., Subramaniam, S. and Scott, H. L. (1999). Optimization of hydrocarbon chain interaction parameters application to the simulation of fluid phase lipid bilayers, J. Phys. Chem. B, 103, 6323-6327. 

The fluorescence energy transfer process has been widely used to determine the distance between fluorophores, the surface density of fluorophores in the lipid bilayer, and the orientation of membrane protein or protein segments, often with reference to the membrane surface and protein-protein interactions. Membranes are intrinsically dynamic in nature, so that so far the major applications have been the determination of fixed distances between molecules of interest in the membrane. 

The successful application of in vitro models of intestinal drug absorption depends on the ability of the in vitro model to mimic the relevant characteristics of the in vivo biological barrier. Most compounds are absorbed by passive transcellular diffusion. To undergo tran-scellular transport a molecule must cross the lipid bilayer of the apical and basolateral cell membranes. In recent years, there has been a widespread acceptance of a technique, artificial membrane permeation assay (PAMPA), to estimate intestinal permeability.117118 The principle of the PAMPA is that, diffusion across a lipid layer, mimics transepithelial permeation. Experiments are conducted by applying a drug solution on top of a lipid layer covering a filter that separates top (donor) and bottom (receiver) chambers. The rate of drug appearance in the bottom wells should reflect the diffusion across the lipid layer, and by extrapolation, across the epithelial cell layer. 

As one increases the size of the cages, the cavity becomes sufficiently large to be used as a nanoreactor. In fact, nanometer size capsules or spheres made of lipid bilayers have been investigated for other applications including drug delivery. However, without modification, such vesicles are probably not suitable as reactors since the lipid bilayer is rather fluid, and the lipid molecules exchange with free lipids in solution. In order to use such vesicles as reactors, it is necessary to convert them into a robust... 

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