Transport mechanisms bilayers

With the adequacy of lipid bilayer membranes as models for the basic structural motif and hence for the ion transport barrier of biological membranes, studies of channel and carrier ion transport mechanisms across such membranes become of central relevance to transport across cell membranes. The fundamental principles derived from these studies, however, have generality beyond the specific model systems. As noted above and as will be treated below, it is found that selective transport... 

Studies of the effect of permeant s size on the translational diffusion in membranes suggest that a free-volume model is appropriate for the description of diffusion processes in the bilayers [93]. The dynamic motion of the chains of the membrane lipids and proteins may result in the formation of transient pockets of free volume or cavities into which a permeant molecule can enter. Diffusion occurs when a permeant jumps from a donor to an acceptor cavity. Results from recent molecular dynamics simulations suggest that the free volume transport mechanism is more likely to be operative in the core of the bilayer [84]. In the more ordered region of the bilayer, a kink shift diffusion mechanism is more likely to occur [84,94]. Kinks may be pictured as dynamic structural defects representing small, mobile free volumes in the hydrocarbon phase of the membrane, i.e., conformational kink g tg ) isomers of the hydrocarbon chains resulting from thermal motion [52] (Fig. 8). Small molecules can enter the small free volumes of the kinks and migrate across the membrane together with the kinks. 

All of the above considerations have sometimes led to a too rigid picture of the membrane structure. Of course, the mentioned types of fluctuations (protrusions, fluctuations in area per molecule, chain interdigitations) do exist and will turn out to be important. Without these, the membrane would lack any mechanism to, for example, adjust to the environmental conditions or to accommodate additives. Here we come to the central theme of this review. In order to come to predictive models for permeation in, and transport through bilayers, it is necessary to go beyond the surfactant parameter approach and the fluid mosaic model. 

Johnson ME, Blankschtein D, Langer R (1997) Evaluation of solute permeation through the stratum corneum lateral bilayer diffusion as the primary transport mechanism. J Pharm Sci 86 1162-1172. 

Drug molecules are transported across cell membranes. Because of the lipid bilayer construction of the membrane (Appendix 2), nonpolar (lipid-soluble) molecules are able to diffuse and penetrate the cell membrane. Polar molecules, however, cannot penetrate the cell membrane readily via passive diffusion and rely on other transport mechanisms. 

Transport mechanisms of the pore type (Fig. 3) seem to be induced (e.g., by amphotericin B) in bilayer membranes and there is very good... 

In the fourth subtechnique, flow FFF (F/FFF), an external field, as such, is not used. Its place is taken by a slow transverse flow of the carrier liquid. In the usual case carrier permeates into the channel through the top wall (a layer of porous frit), moves slowly across the thin channel space, and seeps out of a membrane-frit bilayer constituting the bottom (accumulation) wall. This slow transverse flow is superimposed on the much faster down-channel flow. We emphasized in Section 7.4 that flow provides a transport mechanism much like that of an external field hence the substitution of transverse flow for a transverse (perpendicular) field is feasible. However this transverse flow—crossflow as we call it—is not by itself selective (see Section 7.4) different particle types are all transported toward the accumulation wall at the same rate. Nonetheless the thickness of the steady-state layer of particles formed at the accumulation wall is variable, determined by a combination of the crossflow transport which forms the layer and by diffusion which breaks it down. Since diffusion coefficients vary from species to species, exponential distributions of different thicknesses are formed, leading to normal FFF separation. 

Emphasis is placed here on features of the biological membranes which are implicated in substrate transport. The lipid bilayer in the "gel" state, in the absence of additives, forms an effective barrier against polar ions and water soluble substrates. Changing the fluidity, by phase transition (induced by temperature changes and/or by the addition of foreign ions or molecules) or by the incorporation of additives (cholesterol, for example), profoundly influences the structure and, hence, the transport properties of membranes. This, and the presence of channel or pore forming peptides or proteins, opens the door to a number of transport mechanisms which will be summarized in the following section. 

A more difficult question to pursue is how electron transport occurs [38]. Three types of electron-transport mechanisms across bilayer membranes have been envisioned, including (i) direct electron tunneling from the donor to the acceptor located at the opposite membrane interfaces, (ii) electron carrier-mediated diffusional... 

In order to gain information on the transport mechanism the permeation rates of a number of alkali and alkaline earth metal chlorides, copper, zinc, and lanthanum chloride, and sodium and magnesium sulfate were determined. In an additional experiment, the concentration of the permeating salt solution was varied from 1 mmol L-1 to 3 mol L-1. All measurements were carried out on membranes consisting of 60 PVA/PVS bilayers [76]. 

Surfactant Effects on Microbial Membranes and Proteins. Two major factors in the consideration of surfactant toxicity or inhibition of microbial processes are the disruption of cellular membranes b) interaction with lipid structural components and reaction of the surfactant with the enzymes and other proteins essential to the proper functioning of the bacterial cell (61). The basic structural unit of virtually all biological membranes is the phospholipid bilayer (62, 63). Phospholipids are amphiphilic and resemble the simpler nonbiological molecules of commercially available surfactants (i.e., they contain a strongly hydrophilic head group, whereas two hydrocarbon chains constitute their hydrophobic moieties). Phospholipid molecules form micellar double layers. Biological membranes also contain membrane-associated proteins that may be involved in transport mechanisms across cell membranes. 

The most general water transport mechanism is diffusion through lipid bilayers, with a permeability coefficient of 2-5 x 10 4 cm/sec. The diffusion through lipid bilayers depends on lipid structure and the presence of sterol (Subczyhski et al., 1994). It is suggested that the lateral diffusion of the lipid molecules and the water diffusion through the membrane is a single process (Haines, 1994). 

The advantage of cell culture models is that they are able to measure active transport processes across the cell membranes and not just the interaction of a drug with a lipid bilayer. They can also be used to study passive and active transport routes indeed, much of the knowledge as to the active transport mechanisms in the intestine has been derived from cell culture studies. Despite the predominant route being passive diffusion, the research into transport mechanisms indicates that there are a large number of drugs that are used as substrates for active transporter and efflux systems, and it must therefore be appreciated that multiple transport routes may be involved in the intestinal drug transport. 

MEMBRANE TRANSPORT Membrane transport mechanisms are vital to living organisms. Ions and molecules constantly move across cell plasma membranes and across the membranes of organelles. This flux must be carefully regulated to meet each cell s metabolic needs. For example, a cell s plasma membrane regulates the entrance of nutrient molecules and the exit of waste products. Additionally, it regulates intracellular ion concentrations. Because lipid bilayers are generally impenetrable to ions and polar substances, specific transport components must be inserted into cellular membranes. Several examples of these structures, referred to as transport proteins or permeases, are discussed. 

Some useful theoretical approaches have been developed to describe the noise of many special transport mechanisms, such as ion channels, carriers, and electrogenic pumps (28-33). Unfortunately, there are few experimental studies of transport noise in biological membranes and lipid bilayers. 

See also Passive Transport Mechanisms, Sodium-Potassium Pump, Lipid Bilayer... 

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