Synthetic biological membranes

Because of the heterogeneity of cell membranes, their specific functions are very difficult to study directly. However, from one component, i.e. the lipids, it is possible to construct model systems which can be related to the bioiogica membranes. 

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The structure and funcnonalit of a biological membrane (in this context the plasma or cell membrane) differs fundamentally firom that of a synthetic membrane. A short introduction into the field of biological membranes will be given here in order to first illustrate the considerable difference between these two classes of membrane and secondly because interest in so-called synthetic biological membranes is growing rapidly. For those who are more interested in this field, a number of excellent books and articles may be consulted [see e.g. ref. 23]. 

Simulations of water in synthetic and biological membranes are often performed by modeling the pore as an approximately cylindrical tube of infinite length (thus employing periodic boundary conditions in one direction only). Such a system contains one (curved) interface between the aqueous phase and the pore surface. If the entrance region of the channel is important, or if the pore is to be simulated in equilibrium with a bulk-like phase, a scheme like the one in Fig. 2 can be used. In such a system there are two planar interfaces (with a hole representing the channel entrance) in addition to the curved interface of interest. Periodic boundary conditions can be applied again in all three directions of space. 

Macrocyclic compounds with ion-chelating properties occur naturally and often function as ionophores, translocating ions across biological membranes many of these compounds are small cyclic polypeptides. Some natural carboxylic polyethers are selective for Li+ and are, therefore, ionophores for Li+. Monensin, shown in Figure Id, is a natural ionophore for Na+ but it will also complex with Li+ and it has been shown to mediate the transport of Li+ across phospholipid bilayers [21]. It has been proposed that synthetic Li+-specific ionophores have a potential role as adjuvants in lithium therapy, the aim being to reduce the amount of... 

Let us first consider the lipid molecular structures required. First is the hydrophobic matching. The length of the hydrophobic chain determines the thickness of the hydrophobic part of the lipid bilayer, this should correspond closely to the dimension of the native membrane. As most biological membranes contain diacylglycerol lipids with hydrophobic chain lengths of 16 18 carbon atoms. Thus, synthetic lipids should possess relatively long hydrocarbon chain length, e.g., 16-18 carbon atoms. 

Lipid-protein interactions are of major importance in the structural and dynamic properties of biological membranes. Fluorescent probes can provide much information on these interactions. For example, van Paridon et al.a) used a synthetic derivative of phosphatidylinositol (PI) with a ris-parinaric acid (see formula in Figure 8.4) covalently linked on the sn-2 position for probing phospholipid vesicles and biological membranes. The emission anisotropy decays of this 2-parinaroyl-phosphatidylinositol (PPI) probe incorporated into vesicles consisting of phosphatidylcholine (PC) (with a fraction of 5 mol % of PI) and into acetylcholine receptor rich membranes from Torpedo marmorata are shown in Figure B8.3.1. 

Steroids are derived bio synthetically from cholesterol. They play multiple roles in human physiology sex characteristics, control of inflammation, embryo implantation, and control of salt and water balance. Cholesterol itself is an indispensable constituent of biological membranes. 

The final surfactant structures we consider as models for biological membranes are vesicles. These are spherical or ellipsoidal particles formed by enclosing a volume of aqueous solution in a surfactant bilayer. When phospholipids are the surfactant, these are also known as liposomes, as we have already seen in Vignette 1.3 in Chapter 1. Vesicles may be formed from synthetic surfactants as well. Depending on the conditions of preparation, vesicle diameters may range from 20 nm to 10 pirn, and they may contain one or more enclosed compartments. A multicompartment vesicle has an onionlike structure with concentric bilayer surfaces enclosing smaller vesicles in larger aqueous compartments. 

Polylactones (for an example, see Fig. 14.4) are synthetic analogues of naturally occurring ionophores such as enniatin (species that transport ions across biological membranes). Molecular mechanics calculations have been used to predict the stability and selectivity with respect to Li+, Na+, and K+ of a series of new polylactones12661. Metal-ligand interactions were again modeled using a combination of van der Waals and electrostatic terms. 

Such materials are known as semipermeable membranes. They are essential components of nearly all living things, and the development of new materials of this type is an important component of biomedical research. The control of diffusion of molecules through a membrane can be accomplished by variations in the hydrophilicity of the polymer molecules that constitute the membrane. As in biological membranes, hydrophobic molecules are more likely to pass through the hydrophobic domains of a synthetic membrane than through the hydrophilic regions, and vice versa. 

The first synthetic amphiphiles found to self-organize into bilayers, were quaternary ammonium salts bearing two long alkyl chains 1.13.47.48.49 it is interesting to note that these molecules did not contain a connector moiety between the polar and the apolar part, as in the case of the biolipids. While the physicochemical properties of these bilayers were found to be comparable to those of the biological membranes, the synthetic lipids were found to... 

In biological membranes, integral proteins are amphipatic molecules their hydro-phobic moiety is embedded in the lipid bilayer and their hydrophilic moiety protrudes from the surface of the membrane279. So, it was interesting to prepare polymeric models of such amphipatic proteins. For that purpose, two new classes of block copolymers have been synthetized in Orleans, namely copolymers with a polyvinyl block and a polypeptide block and copolymers with a saccharide and a peptide block. We shall give some information concerning the preparation of these copolymers and then describe their structure. 

A number of enzymes appear therefore to be localized in a specific micro-environment, which can influence. their biocatalytic activity. Because of the complexity of biological membranes, our understanding of the influence of micro-environmental effects on membrane-bound enzyme is minimal. An important contribution to better understanding the mode of action of membrane-bound enzyme has been the development of the concept of heterogeneous catalysis by enzymes synthetically bound to water-insoluble supports. These immobilized enzymes were viewed as models for the cellular bound enzyme (3,A). 

There are many studies of the transfer of electrons from enzymes to substrates, across biological membranes, to (or from) electrodes from (or to) substrates, between adsorbed molecular dyes and semiconductor particles, within synthetic films and nano-scale arrays, within molecular wires , and so on. Only a few, general comments will be offered on these topics here. The basic physics of molecular electron transfer does not change with the scale of the system, as long as identifiable molecular moieties are present with at least partly localized electronic configurations. The nature of the properties observed, the experimental probes available, and the level of theoretical treatment that is useful may be very different. Different approaches, different limiting models are used for extended arrays (or lattices) of very strongly coupled moieties. 

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