Models membranes

This criterion resumes all the a priori knowledge that we are able to convey concerning the physical aspect of the flawed region. Unfortunately, neither the weak membrane model (U2 (f)) nor the Beta law Ui (f)) energies are convex functions. Consequently, we need to implement a global optimization technique to reach the solution. Simulated annealing (SA) cannot be used here because it leads to a prohibitive cost for calculations [9]. We have adopted a continuation method like the GNC [2]. 

Reverse osmosis models can be divided into three types irreversible thermodynamics models, such as Kedem-Katchalsky and Spiegler-Kedem models nonporous or homogeneous membrane models, such as the solution—diffusion (SD), solution—diffusion—imperfection, and extended solution—diffusion models and pore models, such as the finely porous, preferential sorption—capillary flow, and surface force—pore flow models. Charged RO membrane theories can be used to describe nanofiltration membranes, which are often negatively charged. Models such as Dorman exclusion and the... 

A fundamental difference exists between the assumptions of the homogeneous and porous membrane models. For the homogeneous models, it is assumed that the membrane is nonporous, that is, transport takes place between the interstitial spaces of the polymer chains or polymer nodules, usually by diffusion. For the porous models, it is assumed that transport takes place through pores that mn the length of the membrane barrier layer. As a result, transport can occur by both diffusion and convection through the pores. Whereas both conceptual models have had some success in predicting RO separations, the question of whether an RO membrane is truly homogeneous, ie, has no pores, or is porous, is still a point of debate. No available technique can definitively answer this question. Two models, one nonporous and diffusion-based, the other pore-based, are discussed herein. 

L. Fiuegold, ed.. Cholesterol in Membrane Models, CRC Press Inc., Boca Raton, Fla., 1993. 

The most popular theoretical description of the potentiometric behavior of ion-selective membranes makes use of the three-segmented membrane model introduced by Sollner53), Teorell 30,54), and Meyer and Sievers 31-5S). In this model the two phase boundaries and the interior of the membrane are treated separately. Here, the... 

Our first exploration of property space was focused on acetylcholine. This molecule was chosen for its interesting structure, major biological role, and the abundant data available on its conformational properties [15]. The behavior of acetylcholine was analyzed by MD simulations in vacuum, in isotropic media (water and chloroform) [16] and in an anisotropic medium, i.e. a membrane model [17]. Hydrated n-octanol (Imol water/4mol octanol) was also used to represent a medium structurally intermediate between a membrane and the isotropic solvents [17]. 

Conversely, in a membrane model, acetylcholine showed mean log P values very similar to those exhibited in water. This was due to the compound remaining in the vicinity of the polar phospholipid heads, but the disappearance of extended forms decreased the average log P value somewhat. This suggests that an anisotropic environment can heavily modify the conformational profile of a solute, thus selecting the conformational clusters more suitable for optimal interactions. In other words, isotropic media select the conformers, whereas anisotropic media select the conformational clusters. The difference in conformational behavior in isotropic versus anisotropic environments can be explained considering that the physicochemical effects induced by an isotropic medium are homogeneously uniform around the solute so that all conformers are equally influenced by them. In contrast, the physicochemical effects induced by an anisotropic medium are not homogeneously distributed and only some conformational clusters can adapt to them. 

Permeability-pH profiles, log Pe - pH curves in arhficial membrane models (log Pjpp - pH in cehular models), generally have sigmoidal shape, similar to that of log Dod - pH cf. Fig. 3.1). However, one feature is unique to permeabihty profiles the upper horizontal part of the sigmoidal curves may be verhcally depressed, due to the drug transport resistance arising from the aqueous boundary layer (ABL) adjacent to the two sides of the membrane barrier. Hence, the true membrane contribution to transport may be obscured when water is the rate-limiting resistance to transport. This is especially true if sparingly soluble molecules are considered and if the solutions on either or both sides of the membrane barrier are poorly stirred (often a problem with 96-well microhter plate formats). 

Hodgkin and Huxley [81] formulated a membrane model that accounts for K" ", Na" ", and ion leakage channels in squid giant axons [Fig. 22(a)]. The membrane resting potential for each ion species is treated like a battery and the degree to which the channel is open is modeled by a variable resistor. 

H. Noguchi and G. Gompper, Meshless membrane model based on the moving least-squares method, Phys. Rev. E 73, 021903 (2006). 

Our knowledge of biological membrane ultrastructure has increased considerably over the years as a result of rapid advances in instrumentation. Although there is still controversy over the most correct biological membrane model, the concept of membrane structure presented by Davson and Danielli of a lipid bilayer is perhaps the one best accepted [12,13]. The most current version of that basic model, illustrated in Fig. 7, is referred to as the fluid mosaic model of membrane structure. This model is consistent with what we have learned about the existence of specific ion channels and receptors within and along surface membranes. 

The survey of over 50 artificial lipid membrane models (pION) in this chapter reveals a new and very promising in vitro GIT model, based on the use of levels of lecithin membrane components higher than those previously reported, the use of negatively charged phospholipid membrane components, pH gradients, and artificial sink conditions. Also, a novel direction is suggested in the search for an ideal in vitro BBB model, based on the salient differences between the properties of the GIT and the BBB. 

The history of the development of the bilayer membrane model is fascinating, and spans at least 300 years, beginning with studies of soap bubbles and oil layers on water [517-519]. 

Figure 7.2 Danielli-Davson membrane model. A layer of protein was thought to sandwich a lipid bilayer.

The first membrane model to be widely accepted was that proposed by Danielli and Davson in 1935 [528]. On the basis of the observation that proteins could be adsorbed to oil droplets obtained from mackerel eggs and other research, the two scientists at University College in London proposed the sandwich of lipids model (Fig. 7.2), where a bilayer is covered on both sides by a layer of protein. The model underwent revisions over the years, as more was learned from electron microscopic and X-ray diffraction studies. It was eventually replaced in the 1970s by the current model of the membrane, known as the fluid mosaic model, proposed by Singer and Nicolson [529,530]. In the new model (Fig. 7.3), the lipid bilayer was retained, but the proteins were proposed to be globular and to freely float within the lipid bilayer, some spanning the entire bilayer. 

Different tissues have different lipid compositions. The most common lipid components of membranes are PC and PE. Lipid extracts from brain and lung are also rich in PS heart tissue is rich in PG, and liver is rich in PI [567]. Human blood cells, as ghost erythrocytes (with cytoplasm contents removed), are often used as membrane models. These have different compositions between the inner and outer leaflets of the bilayer membrane. Phospholipids account for 46% of the outer leaflet membrane constituents, with PC and Sph about equal in amount. The inner leaflet is richer in phospholipids (55%), with the mix 19% PE, 12% PS, 7% PC and 5% Sph [567],... 

Figure 7.14 Relative concentrations of accetor and donor compartments as a function of time for the thin-membrane model.

Figure 7.15 shows the appearance curves of desipramine and dihydromethysticin [556] in the acceptor wells as a function of time. Because some of the material is lost to the membrane, the curves level off asymptotically at acceptor concentration fractions considerably less the 0.5 value expected in the thin-membrane model (Fig. 7.14). The solid curve for desipramine in Fig. 7.15a is a least-squares fit of the data points to Eq. (7.21), with the parameters Pe 24 x 10-6 cm/s, R 0.13, and xLAG 11 min. The solid curve for dihydromethisticin in Fig. 7.15b is described by the parameters Pe 32 x 10 6 cm/s, R 0.42, and xLAG 35 min.

Figure 7.28b shows that membrane retention is very systematically increased for almost all of the weak bases. This is a general pattern for bases with any of the negatively charged membrane models, and is probably best explained by the increased electrostatic attractions between the drugs and the membranes. Still, all retentions are below 50%, due to the offsetting sink condition created in the acceptor wells. 

The above iso-pH measurements are based on the 2% DOPC/dodecane system (model 1.0 over pH 3-10 range). Another membrane model was also explored by us. Table 7.16 lists iso-pH effective permeability measurements using the soy lecithin (20% wt/vol in dodecane) membrane PAMPA (models 17.1, 24.1, and 25.1) The negative membrane charge, the multicomponent phospholipid mixture, and the acceptor sink condition (Table 7.1) result in different intrinsic permeabilities for the probe molecules. Figure 7.40 shows the relationship between the 2% DOPC and the 20% soy iso-pH PAMPA systems for ketoprofen. Since the intrinsic permeability of ketoprofen in the soy lecithin membrane is about 20 times greater than in DOPC membrane, the flat diffusion-limited transport region of the log Pe... 

Following the original simple concepts of Gorter and Grendel, a large number of membrane models have been developed over the subsequent half a century the two most contrasting are shown in Fig. 6.9. 

Figure 6 Intestinal cell membrane model with integral membrane proteins embedded in lipid bilayer. The phospholipid bilayer is 30-45 A thick, and membrane proteins can span up to 100 A through the bilayer. The structure of a typical phospholipid membrane constituent, lecithin is illustrated. (From Ref. 76.)...

Cantrell et al. (2003) studied the quenching of 02 by several dietary carotenoids in dipalmitoyl phosphatidylcholine (DPPC) unilamellar liposomes. These workers used water soluble and lipid soluble 02 sensitizers so that a comparison of the efficiencies of quenching 02 generated within and outside the membrane model could be made. Perhaps surprisingly there was little difference in the efficiency of quenching in either situation. Typical results are presented in Table 14.3 (taken from Cantrell et al. (2003 and 2006)). 

The aforementioned results refer to unilamellar membrane models but essentially similar results are obtained in multilamellar vesicles, though the kinetics are more complex in such systems. The numerical values observed in these model membranes simply show that one or more of the aforementioned factors arise however, in the in vivo situation, the preeminent effect is unknown but may well be the proximity of the hydroxyl group to the water interface. 

Here, we discuss a solid-state 19F-NMR approach that has been developed for structural studies of MAPs in lipid bilayers, and how this can be translated to measurements in native biomembranes. We review the essentials of the methodology and discuss key objectives in the practice of 19F-labelling of peptides. Furthermore, the preparation of macroscopically oriented biomembranes on solid supports is discussed in the context of other membrane models. Two native biomembrane systems are presented as examples human erythrocyte ghosts as representatives of eukaryotic cell membranes, and protoplasts from Micrococcus luteus as membranes... 

Keywords Solid-state NMR structure analysis 19F-labeling Membrane-active peptides Native biomembranes Oriented membrane models Antimicrobial peptides... 

Fig. 2 Mechanically oriented bilayer samples as a membrane model for ssNMR. (a) Illustration of the hydrated lipid bilayers with MAPs embedded, the glass supports, and the insulating wrapping, (b) A real sample consists of 15 stacked glass slides, (c) Schematic solid-state 19F-NMR lineshapes from an oriented CF3-labelled peptide (red), and the corresponding powder lineshape from a non-oriented sample (grey), (d) Illustration of typical orientational defects in real samples - the sources of powder contribution in the spectra...

To study the structural behaviour of MAPs, an adequate membrane model (see Fig. 5) is essential. Simple organic solvent systems, such as DMSO, MeOH/H20 or TFE/PLO mixtures, present a similar dielectric environment as a membrane on... 

Fig. 5 Membrane models for NMR structure analysis, (a) An isotropic detergent micelle (left) is compared to the dimensions of lipid bilayers (right), (b) Macroscopically oriented membrane samples can be prepared on solid support, as nanodiscs, or as magnetically oriented bicelles. (c) Nomenclature and variability of liposomes small (SUV, 20-40 nm), intermediate (IUV, 40-60 nm), large (LUV, 100-400 nm), and giant unilamellar vesicles (GUV, 1 pm) multi-lamellar (MLV), oligo-lamellar (OLV) and highly heterogeneous multi-oligo-lamellar vesicles (MOLV)...

Compared to the sizes of living cells,1 IUV and LUV resemble the dimensions of enveloped viruses (ranging from 80 to 400 nm) [94], while GUVs resemble typical bacteria and erythrocytes (1-7 pm). Eukaryotic cells tend to be even larger (10-30 pm in animals, 10-100 pm in plants). These dimensions imply that, except for viruses or specific sub-cellular membranes, flat bilayers are the only relevant membrane models. Hence, macroscopically oriented bilayers on solid supports (see... 

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