Membrane bilayer lipid transport across

Proteins embedded in the lipid bilayer of membranes play an important role in membrane functions, involving transport across the bilayer, electron flow and energy conversion, cell recognition, receptor functions, etc. There is not much information available on structural features of these proteins due to difficulties in crystallisation, necessary for complete structure determination. 

PhotocontroUed Transport Phenomenon in Lipid Bilayer Membranes. Photocontrolled ion transport across lipid bilayer membranes using photoresponsive compounds such as azobenzene derivatives has been of great interest for potential applications in optoelectronic devices and optical transducers. Most research has exploited membrane capacitance change because of the disruption of membrane structures resulting from photoisomerization of azoben-zene-containing compounds incorporated into the lipid bilayers. Others have used the volumetric change of azobenzene moieties associated with photoisomerization. 

The possible biological involvement of lipid polymorphism in many events such as membrane fusion, exocytosis, transport across bilayers, and intermembrane connections was extensively discussed by Cullis and de Kniijff (1979) and Cullis et ai (1982). 

The Energetics Problem of Cation Transport Across Lipid Bilayer Membranes A qualitative perspective of the barrier presented by a lipid bilayer membrane can be obtained from the Bom expression2) for solvation energy, SE,... 

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... 

Antonenko, Y. N. Denisov, G. A. Pohl, P., Weak acid transport across bilayer lipid membrane in the presence of buffers, Biophys. J. 64, 1701-1710 (1993). 

In biological systems, one often observes membrane structures with nonzero spontaneous curvatures, e.g. in mitochondria. This type of bilayer structure is also essential in various transport related processes such as endo- and exocy-tosis (see Chapter 8 of this volume). These curved membrane systems may be stabilised by protein aggregation in the bilayer, or may be the result of the fact that biological membranes are constantly kept off-equilibrium by lipid transport and/or by (active) transport processes across the bilayer. These interesting... 

Of course there are many phenomena that equilibrate on the nanosecond timescale. However, the majority of relevant events take much more time. For example, the ns timescale is much too short to allow for the self-assembly of a set of lipids from a homogeneously distributed state to a lamellar topology. This is the reason why it is necessary to start a simulation as close as possible to the expected equilibrated state. Of course, this is a tricky practice and should be considered as one of the inherent problems of MD. Only recently, this issue was addressed by Marrink [56]. Here the homogeneous state of the lipids was used as the start configuration, and at the end of the simulation an intact bilayer was found. Permeation, transport across a bilayer, and partitioning of molecules from the water to the membrane phase typically take also more time than can be dealt with by MD. We will return to this point below. 

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. 

Much interest for ion transport has its origin in the field of crown ether chemistry. Therefore, most model studies of ion channels have been more or less based on crown ether chemistries. Pioneering work has been undertaken by Fylcs, who not only synthesized varieties of gigantic molecules starting from crown ethers, " but established a method of the rate assay for ion transport across lipid bilayer membranes, a pH sCat technique. Vesicles having different inside and outside... 

Figure 13.9. Membrane permeability coefficience of solutes. Solute permeabilities across typical lipid bilayers of liposomes or lipid vesicles are presented as their respective coefficients in cm/s. In the absence of other transport processes, it would require 10 s to move Na+ across 1 cm distance. When there is a concentration difference across a membrane, multiplying the concentration difference (mole/ml equivalent to mole/cm ) by the permeability coefficient (cm/s) allows estimation of flow rate (mole/s-cm ). For example, a concentration difference of 1Q- mole/cm Na (or 1 x 10" M Na ) would provide a flow of 10 mole/cm x 10" cm/s = IQ- mole/s through 1 cm or 0.006 mole/s through 1 pm of a membrane bilayer.

A solution of brain lipids was brushed across a small hole in a 5-ml. polyethylene pH cup immersed in an electrolyte solution. As observed under low power magnification, the thick lipid film initially formed exhibited intense interference colors. Finally, after thinning, black spots of poor reflectivity suddenly appeared in the film. The black spots grew rapidly and evenutally extended to the limit of the opening (5, 10). The black membranes have a thickness ranging from 60-90 A. under the electron microscope. Optical and electrical capacitance measurements have also demonstrated that the membrane, when in the final black state, corresponds closely to a bimolecular leaflet structure. Hence, these membranous structures are known as bimolecular, black, or bilayer lipid membranes (abbreviated as BLM). The transverse electrical and transport properties of BLM have been studied usually by forming such a structure interposed between two aqueous phases (10, 17). 

The transport of molecules across biological cell membranes and biomimetic membranes, including planar bilayer lipid membranes (BLMs) and giant liposomes, has been studied by SECM. The approaches used in those studies are conceptually similar to generation-collection and feedback SECM experiments. In the former mode, an amperometric tip is used to measure concentration profiles and monitor fluxes of molecules crossing the membrane. In a feedback-type experiment, the tip process depletes the concentration of the transferred species on one side of the membrane and in this way induces its transfer across the membrane. 

Ions and small molecules may be transported across cell membranes or lipid bilayers by artificial methods that employ either a carrier or channel mechanism. The former mechanism is worthy of brief investigation as it has several ramifications in the design of selectivity filters in artificial transmembrane channels. To date there are few examples where transmembrane studies have been carried out on artificial transporters. The channel mechanism is much more amenable to analysis by traditional biological techniques, such as planar bilayer and patch clamp methods, so perhaps it is not surprising that more work has been done to model transmembrane channels. 

The Ln(III) cations can be used in another fashion in the study of vesicles as pointed out by Bystrov62. The cations can be contained either only inside or only outside the bilayer as they cannot cross the membrane. Using a shift probe, say Pr(III), on the inside of the vesicle the resonances of the head-group of the inside lipids are shifted relative to those on the outside. It then becomes possible to follow differentially the inside and outside lipid signals on making changes in the bathing solution. This has permitted numerous studies of transport across the lipid bilayer. 

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