Applications biological membranes

Many complex systems have been spread on liquid interfaces for a variety of reasons. We begin this chapter with a discussion of the behavior of synthetic polymers at the liquid-air interface. Most of these systems are linear macromolecules however, rigid-rod polymers and more complex structures are of interest for potential optoelectronic applications. Biological macromolecules are spread at the liquid-vapor interface to fabricate sensors and other biomedical devices. In addition, the study of proteins at the air-water interface yields important information on enzymatic recognition, and membrane protein behavior. We touch on other biological systems, namely, phospholipids and cholesterol monolayers. These systems are so widely and routinely studied these days that they were also mentioned in some detail in Chapter IV. The closely related matter of bilayers and vesicles is also briefly addressed. 

MI SchlenkiTch, I Bnckmann, AD MacKerell Ir, M Karplus. Criteria for parameters optimization and applications. In KM Merz Ir, B Roux, eds. Biological Membranes A Molecular Perspective from Computation and Experiment. Boston Birkhauser, 1996, pp 31-81. 

This volume thus presents a current and comprehensive account of computational methods and their application to biological macromolecules. We hope that it will serve as a useful tool to guide future investigations of proteins, nucleic acids, and biological membranes, so that the mysteries of biological molecules can continue to be revealed. 

Recently, unique vesicle-forming (spherical bUayers that offer a hydrophilic reservoir, suitable for incorporation of water-soluble molecules, as well as hydrophobic wall that protects the loaded molecules from the external solution) setf-assembUng peptide-based amphiphilic block copolymers that mimic biological membranes have attracted great interest as polymersomes or functional polymersomes due to their new and promising applications in dmg delivery and artificial cells [ 122]. However, in all the cases the block copolymers formed are chemically dispersed and are often contaminated with homopolymer. 

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. 

The first two volumes in the series New Comprehensive Biochemistry appeared in 1981. Volume 1 dealt with membrane structure and Volume 2 with membrane transport. The editors of the last volume (the present editor being one of them) tried to provide an overview of the state of the art of the research in that field. Most of the chapters dealt with kinetic approaches aiming to understand the mechanism of the various types of transport of ions and metabolites across biological membranes. Although these methods have not lost their significance, the development of molecular biological techniques and their application in this field has given to the area of membrane transport such a new dimension that the appearance of a volume in the series New Comprehensive Biochemistry devoted to molecular aspects of membrane proteins is warranted. 

Applications Membranes create a boundary between different bulk gas or hquid mixtures. Different solutes and solvents flow through membranes at different rates. This enables the use of membranes in separation processes. Membrane processes can be operated at moderate temperatures for sensitive components (e.g., food, pharmaceuticals). Membrane processes also tend to have low relative capital and energy costs. Their modular format permits rehable scale-up and operation. This unit operation has seen widespread commercial adoption since the 1960s for component enrichment, depletion, or equilibration. Estimates of annual membrane module sales in 2005 are shown in Table 20-16. Applications of membranes for diagnostic and bench-scale use are not included. Natural biological systems widely employ membranes to isolate cells, organs, and nuclei. 

Various types of research are carried out on ITIESs nowadays. These studies are modeled on electrochemical techniques, theories, and systems. Studies of ion transfer across ITIESs are especially interesting and important because these are the only studies on ITIESs. Many complex ion transfers assisted by some chemical reactions have been studied, to say nothing of single ion transfers. In the world of nature, many types of ion transfer play important roles such as selective ion transfer through biological membranes. Therefore, there are quite a few studies that get ideas from those systems, while many interests from analytical applications motivate those too. Since the ion transfer at an ITIES is closely related with the fields of solvent extraction and ion-selective electrodes, these studies mainly deal with facilitated ion transfer by various kinds of ionophores. Since crown ethers as ionophores show interesting selectivity, a lot of derivatives are synthesized and their selectivities are evaluated in solvent extraction, ion-selective systems, etc. Of course electrochemical studies on ITIESs are also suitable for the systems of ion transfer facilitated by crown ethers and have thrown new light on the mechanisms of selectivity exhibited by crown ethers. 

The search for models of biological membranes led to the formation of a separate branch of electrochemistry, i.e. membrane electrochemistry. The most important results obtained in this field include the theory and application of ion-exchanger membranes and the discovery of ion-selective electrodes (including glass electrodes) and bilayer lipid membranes. 

McLaughlin AC, Cullis PR, Hemminga MA, Hoult DI, Radda GK, Ritchie GA, Seeley PJ, Richards RE (1975) Application of 31P NMR to model and biological membrane systems. FEBS Lett 57 213-218... 

By combining bacterial expression and chemical synthesis Ras constructs with the properties of the post-translationally modified protein can be generated. These hybrid proteins can insert into artifical and biological membranes, have been proven to be efficient tools for biochemical, biophysical and biological experiments and can be synthesized in large amounts. Principally the same method is applicable to many of the Ras-related GTP-binding proteins or the y-subunit of heterotrimeric G proteins. 

D. Axelrod, R. M. Fulbright, and E. H. Hellen, Adsorption kinetics on biological membranes Measurement by total internal reflection fluorescence, in Applications of Fluorescence in the Biomedical Sciences (D. L. Taylor, A. S. Waggoner, F. Lanni, R. F. Murphy, and R. Birge, eds.), pp. 461-467, Alan R. Liss, New York (1986). 

Hubbell, W.L., 1990, Transbhayer couphng mechanism for the formation ofhpid asymmetry in biological membranes. Application to the photoreceptor disc membrane. Biophys. J. 57 ... 

Schlenkrich, M., Brickmann, J., MacKerell Jr., A. D., and Karplus, M. (1996) An empirical potential energy function for phospholipids criteria for parameter optimization and application. In Biological membranes a molecular perspective from computational and experiment, Merz Jr., K. M. and Roux, B. (eds.), Birkhauser, Boston, 31-81. 

Reaction engineering helps in characterization and application of chemical and biological catalysts. Both types of catalyst can be retained in membrane reactors, resulting in a significant reduction of the product-specific catalyst consumption. The application of membrane reactors allows the use of non-immobilized biocatalysts with high volumetric productivities. Biocatalysts can also be immobilized in the aqueous phase of an aqueous-organic two-phase system. Here the choice of the enzyme-solvent combination and the process parameters are crucial for a successful application. 

At the most fundamental level, monolayers of surfactants at an air-liquid interface serve as model systems to examine condensed matter phenomena. As we see briefly in Section 7.4, a rich variety of phases and structures occurs in such films, and phenomena such as nucleation, dendritic growth, and crystallization can be studied by a number of methods. Moreover, monolayers and bilayers of lipids can be used to model biological membranes and to produce vesicles and liposomes for potential applications in artificial blood substitutes and drug delivery systems (see, for example, Vignette 1.3 on liposomes in Chapter 1). 

Extensive studies have been carried out concerning ion transfers, electron transfers and combinations of ion and electron transfers at liquid-liquid interfaces. Po-larography and voltammetry at liquid-liquid interfaces are of analytical importance, because they are applicable to ionic species that are neither reducible nor oxidizable at conventional electrodes. They are also usefid in studying charge-transfer processes at liquid-liquid interfaces or at membranes solvent extractions, phase transfer catalyses, ion transport at biological membranes, etc. are included among such processes. 

An outstanding example of the application of the theories and methods of electrochemical kinetics to an apparently different field of high interest in biological science is found in the fundamental investigation of ion transport through biological membranes. Two concise, but very clear reviews on this subject have been written by de Levie [108, 109] references to other reviews and further bibliography can be found therein. 

The points noted in this section are necessarily of a very limited range of vision. Most probably the real biological membrane is of much more complex nature than the artificial model systems. Yet the approaches sketched here may also have initiated the application of electrochemical methods to more practical cases [115]. 

Peptidomimetics have found wide application as biostable, bioavailable, and often potent surrogates of naturally occurring peptides. They form the basis of important families of enzyme inhibitors and they act as receptor agonists and antagonists. Peptide chemists are also gaining a deeper understanding of the structural features of this class of compounds that influence their ability to permeate biological membranes and their pharmacokinetic properties. 

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