Membrane, biological

The plasma membranes of cells are constructed of lipids. Lipids have amphiphilic structure just as soaps and detergent surfactant discussed in Chapter 1. 

Illustration of the piezoelectric response of bilayers (such as cell membrane) to mechanical shear. 

The self-organization of lipids to form plasma membrane was a crucial step in the evolution of the life. Cell membranes demonstrate organic chemistry beyond covalent bonds. It is tiie interplay between molecular selforganization and molecular recognition of its individual constituents, which 

In view of fhe discussions of the previous chapters we can easily realize that the cell membranes are piezoelectric and flexoelectric. A mechanical shear would locally cause a tilt, which, due to the chirality of the molecules, leads to the appearance of macroscopic dipole moment, just as was described for SmA materials in the previous chapter. 

Interacting living amoeboid cells themselves form nematic liquid crystals phases. It was observed that (1) a cluster of a polar nematic liquid crystal is formed by cells, which emit molecules for attracting other cells, and 

Biological membranes are considerably more complex than the models discussed above for electrode/aqueous electrolyte interfaces and there might appear to be few lines of comparison to be drawn between the two cases. Biomembranes possess two-dimensional structure and have a thickness of approximately 100 angstroms. They are formed primarily from amphiphilic phospholipids, which impart the two-dimensional structure to the membrane, and from proteins. In aqueous solutions, the long hydrophobic tails of the lipids are found in the interior of the membrane while the polar head 

Another similarity between the interfaces of electrodes and biomembranes in contact with aqueous solutions is the existence of an ordered water layer at their respective surfaces. Considerable attention has been given to understanding the structure of water at biomembrane surfaces. Studies of 

Electrode/aqueous electrolyte interfaces lack the molecular specificity associated with biomembranes in controlling the enzymatic character of biological redox reactions. However, the interfacial role in biological electron transfer reactions can still be probed by electrochemical techniques. This is not an ideal situation but it does offer some advantages over experiments in which reaction partners are studied under conditions in which the two-dimensional nature of the membrane is entirely lost. 

The determination of the thermodynamics of an electron transfer reaction relies on the experimental constraints that were discussed in the Introduction section. The reliable determination of the formal potential of a redox couple is dependent upon the observation of responses which are Nernstian. For the redox process given by 

Certain advantages arise in the use of electrochemical techniques compared to chemical redox titrations in the determination of biological molecule thermodynamic parameters. Electrochemical techniques which couple the principle of mediation between electrodes and biological molecules to overcome irreversible electrode reactions with optical monitoring of the redox state of the sample have recently been developed. The following two sections address the principles and applications of these techniques in the study of biological molecule thermodynamics. 

Lipid bilayers are of fundamental importance in biology. All biological membranes are formed by lipid bilayers. They separate the interior of cells from the outside world and they separate different compartments in eucaryontic cells. Why are they such ideal structures for membranes Their main task is to avoid diffusion of polar molecules (such as sugars, nucleotides) and ions (in particular Ca2+, Na+, K+, and CP) from one compartment into another. The hydrophobic interior of the lipid bilayers efficiently achieves this. Polar molecules and especially ions cannot pass the hydrophobic interior. To transfer, for instance, an ion of radius R = 2 A from the water phase (ei = 78) into a hydrocarbon environment ( 2 = 4) the change in Gibbs free energy is [535] 

This is 33 kBT and ions have practically no chance to pass the interior of a lipid membrane. As a result the electric resistivity of a lipid bilayer in aqueous electrolyte is extremely high. In general, the electrical resistivity of a membrane Re is inversely proportional to its area A  

Rmem is the specific membrane resistance in units of wcm2. For lipid bilayers Rmem is of the order of 108 flcm2. If we built a membrane of similar thickness ( 4 nm) of a good insulator like porcelaine (specific resistivity 1014 flcm) its membrane resistance would only be 1014 Qcrn. 10-7 cm = 107 flcm2. In addition, a bilayer can stand potentials of typically 200 mV, which results in an enormous electric field strength of 108 V/m. 

One of the key functions of a membrane is to control the passage of substances across it. They are said to be selectively permeable. The different membranes of the cell have different selective permeabilities. 

Hydrophobic interactions provide the primary driving force for the formation of bilayers (Fig. 3.3). 

Saturated fatty acid chains pack easily and have a higher melting temperature (Tm). Butter is a solid at room temperature so has a high Tm. 

Unsaturated fatty acids have a lower Tm. Canola oil is a liquid at room temperature so has a low Tm. 

Cholesterol impedes motion of the hydrocarbon tails making membranes less fluid (3.4). 

There has been a dramatic increase in interest in the molecular structure of biological membranes. While model systems composed of artificially prepared (or isolated) amphiphilic materials and associated colloids serve a very useful purpose, a 

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]. 

Biological membranes or cell membranes have very complex structures because they must be able to accomplish specific functions. However, a characteristic of various cell membranes is that they contain a basic lipid bilayer structure. Each lipid molecule possess a hydrophobic and a hydrophilic part. A schematic drawing of such a lipid bilayer is given in figure II - 34. This structure exists in different types of cell membrane, the polar pan being situated at the water/membrane interface with the hydrophobic part being 

These lipid bilayers are not very permeable towards a variety of molecules. Nevertheless, for cell metabolism and growth to occur, molecules such as sugars and amino acids must enter the ceil. Specific transport of this type is accomplished by proteins which are incorporated within the bilayer membrane. The protein serves as a carrier and the tjrpe of transport can be defined as carrier-mediated transport. The cell membrane consists of two main components the lipid bilayer which is the backbone, whereas the proteins take care of the specific transport functions. Some of the proteins are located on the outside of the lipid bilayer (the extrinsic proteins), whereas other proteins (the intrinsic proteins), completely penetrate through the lipid bilayer. The intrinsic proteins especially 

Another charaaeiistic feature of transport is that the carrier can be very specific. For example, the carrier in the membrane of the red blood cell (erythrocyte) dtat controls the transport of glucose does not allow the passage of fructose. 

Three different types of passive carrier-mediated transport mechanism may be distinguished similar to transport in liquid membranes (see chapter VI) i) fiicilitated diffusion ii) co-transport and iii) counter-transport. 

Lipids are another type of biomolecule that are very important for life. There are many different kinds of lipids with very different chemical properties, but they all share the property of being insoluble in water. Examples of lipids include fats, oils, waxes, and steroids. Lipids make up the membranes that surround cells. Fats are one of the major food groups because of their very high energy value. 

Triglycerides are the chemical form in which most fat exists in food as well as in the body. A triglyceride is made up of a three-carbon molecule called glycerol, which is bonded to three fatty acids. Fatty acids contain long chains of 12 to 24 carbon atoms. The carbons in fatty acids are bonded to varying numbers of hydrogen atoms. 

Liquid triglycerides are called oils and are found chiefly in plants, although triglycerides from fish are also mostly oils. Triglycerides 

Phospholipids are like triglycerides, but they have two fatty acid chains called tails and one charged group called the head that contains phosphate and oxygen atoms. Because it is charged, the head is polar and therefore attracts water molecules. 

The long fatty acid tail is nonpolar and does not attract water molecules. The polar and nonpolar parts of phospholipids allow them to form lipid bilayers. Bi is from Latin and means two. The bilayer forms when the phospholipid molecules arrange themselves in two layers with the tails facing in (facing each other) and the heads facing out. The result is a phospholipid bilayer that has the tails buried inside and the polar atoms of the heads facing out, where they can form H bonds with water and other molecules. 

Cell membrane lipids are natural surfactants and display most of the properties of synthetic surfactants. The principal difference between these molecules and the surfactants that we discussed above in the chapter is that lipids contain two hydrocarbon tails per molecule. Table 8.5 shows the general structural formula of these cell membrane lipids and the names and formulas for some specific polar head substituents. The alkyl groups in these molecules are usually in the C 6-C24 size range and may be either saturated or unsaturated. 

Much of our understanding of the chemical aspects of cell membranes has been derived from model systems based on surfactants, especially membrane lipids. In this section we are primarily concerned with the use of monolayers, bilayers, and especially black lipid membranes and vesicles as cell membrane models. 

Fundamental membrane research has benefited greatly from the study of monolayers. One of the most important discoveries from this sort of research is the very existence of two-dimensional phases and phase transitions. Generally, studies of the sort that can be carried out with monolayers and bilayers cannot be directly extended to living cells, but some exceptional cases have shown that the extrapolation is valid. For example, it is known from monolayer studies that the presence of unsaturated hydrocarbon chains in lipid monolayers prevents some phase transitions from occurring as the temperature is lowered. Certain mutants of Escherichia coli are unable to synthesize fatty acids and hence can be manipulated through the compounds they are provided as nutrients. Abnormal levels of saturated hydrocarbon can 

15 Schematic representation of a biological membrane. The amphipathic phospholipid molecules form a bilayer with protein molecules embedded in it. (Redrawn, with permission, from S. J. Singer and G. L. Nicolson, Science, 175, 720 (1972).) 

TABLE 8.5 Names and Structures of Some Typical Phospholipid Surfactants 

Despite the weakness and short-range nature of protein-lipid and lipid-lipid interactions, cells have nevertheless evolved means of laterally assembling into membrane-mi-crodomains. Sphingolipid-cholesterol rafts serve to recmit a specific set of membrane proteins and exclude others [24]. Caveolae are deeply invaginated raft domains that are stabilized by caveolin protein oligomers (binding cholesterol) [25]. 

The cell surface additionally displays receptors responsible for cell-cell recognition [28]. Members of this class of receptors are selectins [29] that recognize specific carbohydrates from other cells in the presence of calcium. Other cell surface receptors belong to the immunoglobulin superfamily (IgSF) [30] that promote calcium-independent cell-cell adhesion. The third important class are the calcium-dependent cell adhesion molecules, the cadherins [31], which form dimers with cadherin molecules presented on the surfaces of other cells and hence promote aggregation of similar cell types. 

From the information given above it is obvious that cell surfaces display an enormous complexity. A perfect model to study the interaction of a peptide with a biological membrane would require knowledge about the cell membrane composition in that particular tissue. Even if such information were available it will most probably not be possible to fully mimic the biological environment. However, some important aspects may still be studied with the available models. Whenever possible, one should try to relate the information derived from such a model to information gained from biological data taken on real cells (cell-lines) such as binding affinities etc. in order to prove the validity of the model for the study of a particular aspect. 

A system in a state of criticality has one essential property which explains the term creative used above. This property is the processing of information, whereby 

There are two classes of sins — those of omission and of comission. When it comes to scientific nomenclature, these are clearly sins of Commission  

FIGURE 3.26 (a) Stearic and oleic acid, (b) glycerol and a triglyceride, (c) the general structure of a glycerophospholipid, and (d) the 

FIGURE 3.27 Schematic diagram of a plasma membrane. (Adapted from Voet Voet, 2004.) 

The enzyme which brings about this particular interconversion is known as lactate dehydrogenase, and is normally found associated with NAD , which is said to be its coenzyme. This reaction is further discussed on p. 433. 

It was originally assumed that the composition of a cell, such as an erythrocyte (red blood cell), was more or less uniform throughout—its surface having the same character as its interior. However, a number of investigations made it clear that such cells are surrounded by a membrane which has distinctly different properties from the interior of the cell. At first, it was thought that this membrane was composed entirely of lipid material, but then it was discovered that protein is present also. 

While these models have been very valuable and must be dose to the truth, they need further modification in detail to explain some of the behavior observed. For example, water molecules and ions pass through membranes much more rapidly than would be possible if the structure were exactly as represented in these models. It is necessary to assume in addition that membranes contain water-filled pores along which 

1 The amino acid serine contains 13.33 percent of nitrogen (at. wt. 14.01), and the osmotic pressure method gives an approximate molecular weight of 100. Obtain a more precise value for the molecular weight. 

2 The following are the percentages of iron and sulfur (other than disulfide sulfur) found in pig hemoglobin  

Myelin is the lipid-rich membrane sheath that surrounds the axons of nerve cells it has a particularly high content of sphingomyelins. It consists of many layers of plasma membrane thathave been wrapped around the nerve cell. 

Lipids are frequently open-chain compounds with a polar head group and a long nonpolar tail. 

Glycerol, fatty acids, and phosphoric acid are frequently obtained as degradation products of lipids. 

Another class of lipids consists of fused-ring compounds called steroids. 

Every cell has a cell membrane (also called a plasma membrane) eukaryotic cells also have membrane-enclosed organelles, such as nuclei and mitochondria. The molecular basis of the membrane s structure lies in its hpid and protein components. Now it is time to see how the interaction between the hpid bhayer and membrane proteins determines membrane function. Membranes not only 

FIGURE 15.14. Surfactant molecules containing polymerizable functionalities can be used to produce crosslinked vesicles for microencapsulation. The reactive functionality can be located at the extreme end of the hydrophobic tail (a), in the middle of the tail (b), or closely associated with the hydrophilic head group (c). 

The general approach used to attain such structures has been the synthesis of conventional vesicle-forming amphiphilic materials containing polymerizable functionalities in the molecule, vesicle formation, and subsequent polymerization, preferably by some nonintrusive means such as irradiation. In principle, the polymerizable functionality can be located at the end of the hydrophobic tail, centrally within the tail, or in association with the ionic or polar head group (Fig. 15.14). The choice of a preferred structure will probably be determined by the final needs of the system and the synthetic availability of the desired materials. 

In the last few years there has been a dramatic increase in interest in the molecular structure of biological membranes. While model systems composed of artificially prepared (or isolated) amphiphihc materials and associated colloids serve a very useful purpose, a better understanding of the reality of biological systems would be invaluable in many areas of biochemistry, medicine, pharmaceuticals, and other fields. While it is reasonably easy to determine the constituents of a biological membrane, elucidating just how the various components are put together, how they interact, and their exact function within the membrane represents a decidedly more difficult task. 

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The study of mixed films has become of considerable interest. From the theoretical side, there are pleasing extensions of the various models for single-component films and from the more empirical side, one moves closer to modeling biological membranes. Following Gershfeld [200], we categorize systems as follows ... 

As a point of interest, it is possible to form very thin films or membranes in water, that is, to have the water-film-water system. Thus a solution of lipid can be stretched on an underwater wire frame and, on thinning, the film goes through a succession of interference colors and may end up as a black film of 60-90 A thickness [109]. The situation is reminiscent of soap films in air (see Section XIV-9) it also represents a potentially important modeling of biological membranes. A theoretical model has been discussed by Good [110]. 

Knoll G and Plattner H 1989 Ultrastructural analysis of biological membrane fusion and a tentative correlation with biochemical and biophysical aspects Electron Microscopy of Subcellular Dynamics ed H Plattner (London CRC) pp 95-117... 

Cramer W A and Knaff D B 1990 Energy Transduction in Biological Membranes (New York Springer)... 

Biological membranes provide the essential barrier between cells and the organelles of which cells are composed. Cellular membranes are complicated extensive biomolecular sheetlike structures, mostly fonned by lipid molecules held together by cooperative nonco-valent interactions. A membrane is not a static structure, but rather a complex dynamical two-dimensional liquid crystalline fluid mosaic of oriented proteins and lipids. A number of experimental approaches can be used to investigate and characterize biological membranes. However, the complexity of membranes is such that experimental data remain very difficult to interpret at the microscopic level. In recent years, computational studies of membranes based on detailed atomic models, as summarized in Chapter 21, have greatly increased the ability to interpret experimental data, yielding a much-improved picture of the structure and dynamics of lipid bilayers and the relationship of those properties to membrane function [21]. 

KM Merz Jr, B Roux, eds. Biological Membranes A Molecular Perspective from Computation and Experiment. Boston Birkhauser, 1996. 

Hydrated bilayers containing one or more lipid components are commonly employed as models for biological membranes. These model systems exhibit a multiplicity of structural phases that are not observed in biological membranes. In the state that is analogous to fluid biological membranes, the liquid crystal or La bilayer phase present above the main bilayer phase transition temperature, Ta, the lipid hydrocarbon chains are conforma-tionally disordered and fluid ( melted ), and the lipids diffuse in the plane of the bilayer. At temperatures well below Ta, hydrated bilayers exist in the gel, or Lp, state in which the mostly all-trans chains are collectively tilted and pack in a regular two-dimensional... 

B Roux, TB Woolf. Molecular dynamics of Pfl coat protein in a phospholipid bilayer. In KM Merz Ir, B Roux, eds. Biological Membranes A Molecular Perspective from Computation and Experiment. Boston Birkhauser, 1996, pp 555-587. 

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. 

Langmuir-Blodgett films (LB) and self assembled monolayers (SAM) deposited on metal surfaces have been studied by SERS spectroscopy in several investigations. For example, mono- and bilayers of phospholipids and cholesterol deposited on a rutile prism with a silver coating have been analyzed in contact with water. The study showed that in these models of biological membranes the second layer modified the fluidity of the first monolayer, and revealed the conformation of the polar head close to the silver [4.300]. 

The proportion of ionized and unionized forms of a chemical compound can be readily calculated according to the above equation. It can be easily seen that pK is also a pH value at which 50% of the compound exists in ionized form. The ionization of weak acids increases as the pH increases, whereas the ionization of weak bases increases when the pH decreases. As the proportion of an ionized chemical increases, the diffusion of the chemical through the biological membranes is greatly impaired, and this attenuates toxicokinetic processes. For example, the common drug acetosalicylic acid (aspirin), a weak acid, is readily absorbed from the stomach because most of its dose is in an unionized form at the acidic pH of the stomach. 

After absorption, a chemical compound enters the circulation, which transfers it to all parts of the body. After this phase, the most important factor affecting the distribution is the passage of the compound through biological membranes. From the point of view of the distribution of a chemical compound, the organism can be divided into three different compartments (1) the plasma compartment (2) the intercellular compartment and (3) the intracellular compartment. In all these compartments, a chemical compound can be bound to biological macromolecules. The proportion of bound and unbound (free) chemical compound depends on the characteristics of both the chemical... 

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. 

C. Tanford. The Hydrophobic Effect Formation of Micelles and Biological Membranes. New York Wiley, 1980. 

The double bonds found in fatty acids are nearly always in the cis configuration. As shown in Figure 8.1, this causes a bend or kink in the fatty acid chain. This bend has very important consequences for the structure of biological membranes. Saturated fatty acid chains can pack closely together to form ordered, rigid arrays under certain conditions, but unsaturated fatty acids prevent such close packing and produce flexible, fluid aggregates. 

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