Lipid bilayer membranes conductivities

General anesthetics are usually small solutes with relatively simple molecular structure. As overviewed before, Meyer and Overton have proposed that the potency of general anesthetics correlates with their solubility in organic solvents (the Meyer-Overton theory) almost a century ago. On the other hand, local anesthetics widely used are positively charged amphiphiles in solution and reversibly block the nerve conduction. We expect that the partition of both general and local anesthetics into lipid bilayer membranes plays a key role in controlling the anesthetic potency. Bilayer interfaces are crucial for the delivery of the anesthetics. 

Kasianowicz et al. [65] described the determination of the transport of niclosamide protons across lipid bilayer membranes by equilibrium dialysis, electrophoretic mobility, membrane potential, membrane conductance, and spectrophotometric... 

Thus, the caroviologen approach does produce functional molecular wires that effect electron conduction in a supramolecular-scale system. Incorporation into black lipid bilayer membranes (BLM) should allow further investigations of the electron-transfer properties of these caroviologens and positive preliminary results have been obtained [8.145a]. A theoretical investigation of electron conduction in molecular wires has been made [8.145b]. 

A parallel development came from studies on artificial lipid bilayer membranes. Hladky and Hay don (1984) found that when very small amounts of the antibiotic gramicidin were introduced into such a membrane, its conductance to electrical current flow fluctuated in a stepwise fashion. It looked as though each gramicidin molecule contained an aqueous pore that would permit the flow of monovalent cations through it. Could the ion channels of natural cell membranes act in a similar way To answer this question, it was first necessary to solve the difficult technical problem of how to record the tiny currents that must pass through single channels. 

The frequency response of various chemical constituents of nerve membrane was studied. Biological membranes in general consist of lipids and proteins. Firstly, impedance characteristics of artificial lipid bilayer membranes are examined using lecithin-hexadecane preparations. It was observed that the capacitance of plain lipid membranes was independent of frequency between 100 Hz and 20 KHz. Moreover, application of external voltages has no effect up to 200 mV. Secondly, membrane capacitance and conductance of nerve axon were investigated. There are three components in nerve membranes, i.e., conductance, capaci-... 

CNTs and other nano-sized carbon structures are promising materials for bioapplications, which was predicted even previous to their discovery. These nanoparticles have been applied in bioimaging and drag delivery, as implant materials and scaffolds for tissue growth, to modulate neuronal development and for lipid bilayer membranes. Considerable research has been done in the field of biosensors. Novel optical properties of CNTs have made them potential quantum dot sensors, as well as light emitters. Electrical conductance of CNTs has been exploited for field transistor based biosensors. CNTs and other nano-sized carbon structures are considered third generation amperometric biosensors, where direct electron transfer between the enzyme active center and the transducer takes place. Nanoparticle functionalization is required to achieve their full potential in many fields, including bio-applications. 

Figure 4. Projection of a three-dimensional model of an electrically conducting pore of gramicidin A. To span the full thickness of the lipid bilayer membrane, two molecules, end-to-end, are required. The side chains of the amino acids are not shown. The model was originally proposed by Urry Proc. Nat. Acad. Sci. USA 68, 672 (1971). Reproduced with permission from Ref. 4. Copyright 1983, Springer-Verlag.

The results of permeability studies of lipid vesicles and electrical-conductance measurements of planar bilayers have shovm that lipid bilayer membranes have a very low permeability for ions and most polar molecules. Water is a conspicuous exception to this generalization it readily traverses such membranes because of its small size, high concentration, and lack of a complete charge. The range of measured permeability coefficients is very wide (Figure 12.15). For example, Na+ and K+ traverse these membranes 10 times as slowly as does H2O. Tryptophan, a zwitterion... 

Cold sensitivity. Some antibiotics act as carriers that bind an ion on one side of a membrane, diffuse through the membrane, and release the ion on the other side. The conductance of a lipid-bilayer membrane containing a carrier antibiotic decreased abruptly when the temperature was lowered from 40°C to 36°C. In contrast, there was little change in conductance of the same bilayer membrane when it contained a channel-forming antibiotic. Why ... 

Ion-selective electrodes are another example for interesting methods to analyze synthetic ion channels and pores in LUVs that are arguably less developed and less frequently used. Conductance experiments in supported lipid bilayer membranes may be mentioned as well [20]. 

Fig. 19. Conductance transitions in a lipid bilayer membrane containing gramicidin A. The aqueous solution was 0.5 M NaCl and the applied potential was 100 mV [Reproduced from Hladky, S. B., et al. Ann. Rev. Phys. Chem. 1974, 11.]...

THE NATURE OF THE PERMEABILITY BARRIER AND THE BASIC MECHANISM of ion permeation are understood only in the most general sense even though the first measurements of ionic flux across lipid bilayer membranes were conducted 25 years ago. Establishing a permeation mechanism is difficult because the fluid lipid bilayer is described in terms of average motions of... 

The first question concerns the physical nature of such a channel in the F0 subunit. A useful model is provided by the work of Lear et al. (37, 38), who found that synthetic serine-leucine peptides form ion-conducting channels in planar lipid membranes. The channels apparently are produced when a-helical configurations of the peptides form clusters within the bilayer. For instance, when a 21 residue peptide H2N—(LSSLLSL)3—CONH2 was incorporated into a planar lipid bilayer membrane, channels appeared that had cation conducting properties that resembled those of the acetylcholine... 

In the lipid bilayer systems, since the membrane molecules are arranged in such a way that the charged groups face a water phase and the interior of the membrane is a hydrocarbon phase, the contribution of surface potential to the membrane potential is important. It should be mentioned that the contribution of surface potential to the membrane potential, as discussed above, is generally a transient one in these systems. However, since the electrical conductance due to ion permeation across the lipid bilayer membrane is very low, we can observe the transient potential difference as a quasi-steady state phenomenon. However, if a constant ion distribution is restored by a transport process with a nonelectrical current (active transport) and maintained continuously, the above membrane potential process could become a steady state process. 

Figure 10. Specific conductance of a lipid bilayer membrane as a function of gramicidin concentration in the surrounding solution.

Triton extracts of gastric mucosa contain apparently three materials which can produce channels in lipid bilayers with conductances of 2.5 X 10 ° mho. One material is apparently neutral and cation-selective, another charged, voltage-dependent and anion-selective, whilst the third is non-selective [41]. Material which produces K -selective channels in bilayers has been extracted from excitable tissue [42]. The data obtained so far with these natural channel formers are relatively crude compared with the elegant studies with channel-fdrming antibiotics. Therefore, it is, as yet, unclear whether these materials have definitive roles in biological membrane permeability. 

All these facts have been established on planar lipid bilayers. Experiments conducted on biological membranes using the patch method showed that all regularities in both systems were identical. 

Because of their advanced level of development, high sensitivity, and broad applicability, fluorescence spectroscopy with labeled LUVs and planar bilayer conductance experiments are the two techniques of choice to study synthetic transport systems. The broad applicability of the former also includes ion carriers, but it is extremely difficult to differentiate a carrier from a channel or pore mechanism by LUV experiments. However, the breadth and depth accessible with fluorogenic vesicles in a reliable user-friendly manner are unmatched by any other technique. Planar bilayer conductance experiments are restricted to ion channels and pores and are commonly accepted as substantial evidence for their existence. Exflemely informative, these fragile single-molecule experiments can be very difficult to execute and interpret. Another example for alternative techniques to analyze synthetic transport systems in LUVs is ion-selective electrodes. Conductance experiments in supported lipid bilayer membranes may be mentioned as well. Although these methods are less frequently used, they may be added to the repertoire of the supramolecular chemist. 

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