Lipid bilayer diffusion series

In the same vein, the variation of the diffusion coeflBcient of species across the lipid membrane cannot be explained by employing hydrodynamic expressions, such as the Stokes-Einstein relation. Here one would need to consider the free-energy barrier for entrance into the layer for each species, charged (positive or negative) and neutral the free-energy barrier is expected to be different even for same-sized species. The lipid bilayer diffusion series (LBDS) given by Eq. (12.2) is a manifestation of such microscopic effects. 

Specification of. S SkCG, CO) requires models for the diffusive motions. Neutron scattering experiments on lipid bilayers and other disordered, condensed phase systems are often interpreted in terms of diffusive motions that give rise to an elastic line with a Q-dependent amplitude and a series of Lorentzian quasielastic lines with Q-dependent amplitudes and widths, i.e.. 

One of the key parameters for correlating molecular structure and chemical properties with bioavailability has been transcorneal flux or, alternatively, the corneal permeability coefficient. The epithelium has been modeled as a lipid barrier (possibly with a limited number of aqueous pores that, for this physical model, serve as the equivalent of the extracellular space in a more physiological description) and the stroma as an aqueous barrier (Fig. 11). The endothelium is very thin and porous compared with the epithelium [189] and often has been ignored in the analysis, although mathematically it can be included as part of the lipid barrier. Diffusion through bilayer membranes of various structures has been modeled for some time [202] and adapted to ophthalmic applications more recently [203,204]. For a series of molecules of similar size, it was shown that the permeability increases with octa-nol/water distribution (or partition) coefficient until a plateau is reached. Modeling of this type of data has led to the earlier statement that drugs need to be both... 

FIGURE 19-9 IMADH ubiquinone oxidoreductase (Complex I). Complex I catalyzes the transfer of a hydride ion from NADH to FMN, from which two electrons pass through a series of Fe-S centers to the iron-sulfur protein N-2 in the matrix arm of the complex. Electron transfer from N-2 to ubiquinone on the membrane arm forms QH2, which diffuses into the lipid bilayer. This electron transfer also drives the expulsion from the matrix of four protons per pair of electrons. The detailed mechanism that couples electron and proton transfer in Complex I is not yet known, but probably involves a Q cycle similar to that in Complex III in which QH2 participates twice per electron pair (see Fig. 19-12). Proton flux produces an electrochemical potential across the inner mitochondrial membrane (N side negative, P side positive), which conserves some of the energy released by the electron-transfer reactions. This electrochemical potential drives ATP synthesis. 

Numerous studies support the idea that drug molecules are absorbed through lipid bilayer membranes in the un-ionized state by the process of passive diffusion. The rate of absorption,the pX of the diffusingsolute, and the pH at the absorption site are interrelated. Equation 8.8 demonstrates that the absorption rate of solutes through biological membranes is directly proportional to the value of the oil/water partition coefficient. Houston et al. (16) studied the absorption of a series of carbamate esters through rat everted intes-... 

In contrast to surfactants, lipids adsorbed on hydrophilic surfaces can be expected to form planar bilayers, due to their large spontaneous radius of curvature. A double chain amphiphile forming a bilayer on silica was already discussed in chapter 3.1.2 in the context of 2H NMR investigations of water soluble amphiphiles. Bilayers from water insoluble lipid amphiphiles have been adsorbed to large spherical silica particles by condensation of unilamellar vesicles from aqueous solution, and a series of studies explored different NMR methods suitable for the measurement of lateral diffusion coefficients in such supported bilayers . 

A new series of studies [84] has focused on bilayers composed of unsaturated lipids. This was motivated in part by the fact that (1) bilayer permeability to glycerol was previously found to increase with lipid unsaturation [8] and (2) the solubility of water in alkenes is slightly greater than in alkanes. Transport of various molecules across the bilayer occurs by diffusion down a concentration gradient. The permeability, that characterizes this mass transfer is a property of the membrane composition, the solute, and the temperature,... 

A second series of papers was published by Stouch and co-workers. Bassolino-Klimas et al. calculated diffusion coefficients for benzene molecules in a DMPC bilayer as function of their location in the bilayer. In later papers this work was extended to study the effect of different temperatures on the preferred locations of benzene molecules and the effect of solute size, studying a drug analog. Simulations of permeation and diffusion through and in bilayers will be described more elaborately in Permeation of Lipid Membranes Molecular Dynamics Simulations. 

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