Permeation of lipid membranes

Water-membrane interfaces are discussed separately in this volume (see Environment of a Membrane Protein Molecular Dynamics Studies of Lipid Bilayers and Permeation of Lipid Membranes Molecular Dynamics Simulations). 

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. 

PERMEATION OF LIPID MEMBRANES MOLECULAR DYNAMICS SIMULATIONS... 

Permeation of Lipid Membranes Molecular Dynamics Simulations... 

Figures 4.2b, 4.3b, and 4.4b are log-log speciation plots, indicating the concentrations of species in units of the total aqueous sample concentration. (Similar plots were described by Scherrer [280].) The uppermost curve in Fig. 4.2b shows the concentration of the uncharged species in octanol, as a function of pH. If only uncharged species permeate across lipid membranes, as the pH-partition hypothesis...

I would like to extend Prof. Simon s characterizations of these beautiful new molecules to include a description of the effects on lipid bilayers of his Na+ selective compound number 11, which my post-doctoral student, Kun-Hung Kuo, and I have found to induce an Na+ selective permeation across lipid bilayer membranes [K.-H. Kuo and G. Eisenman, Naf Selective Permeation of Lipid Bilayers, mediated by a Neutral Ionophore, Abstracts 21st Nat. Biophysical Society meeting (Biophys. J., 17, 212a (1977))]. This is the first example, to my knowledge, of the successful reconstitution of an Na+ selective permeation in an artificial bilayer system. (Presumably the previous failure of such well known lipophilic, Na+ complexing molecules as antamanide, perhydroan-tamanide, or Lehn s cryptates to render bilayers selectively permeable to Na+ is due to kinetic limitations on their rate of complexation and decomplexation). 

Fourth, the oxidant and the reductant resulting from the transmembrane PET should not react with the gaseous products of water cleavage (dihydrogen and dioxygen) which can readily permeate through lipid membranes. 

The passive permeability of lipid membranes is another fluidity related parameter. In general, two mechanisms of membrane permeability can operate in the membrane (8). For many nonpolar molecules, the predominant permeation pathway is solubility-diffusion, which is a combination of partitioning and diffusion across the bilayer, both of which depend on lipid fluidity. In a few cases, such as permeation of positively charged ions through thin bilayers, an alternative pathway prevails (9, 10). It is permeation through transient pores produced in the bilayer by thermal fluctuations. This mechanism, in general, correlates with membrane fluidity. However, for model membranes undergoing the main phase transition, permeation caused by this mechanism exhibits a clear maximum near the phase transition point (11). 

Fig. 13 This schematic is a depiction of the two models that are associated with ion permeation through lipid membranes containing some HSA (10-hydroxystearic acid) (smaller headgroup and one hydroxylated acyl chain). The lipids are represented by larger headgroups and two acyl chains, and are shown to form two zones that are rich in lipid, and which differ in density (phase domains). Conductivity through zone A is by electrostatic stabilization of ions occur by hydroxyl moieties that exist in domains that are rich in HSA. Conductivity in zone B also involves stabilization of charge by hydroxyl moieties, but it also shows the steric disorder that can exist between domains. This figure is published with permission (Nikolelis et al. 1991)...

Permeation process of small molecules across lipid membranes studied by molecular dynamics simulations. J. Phys. Chem. 100 (1996) 16729-16738. 

FIG. 13 A schematic illustration of the effects of the free surface area of lipid bilayer membranes on the permeation of two permeants with the same molecular volume, but different cross-sectional areas, (a) A lower free surface area, (b) A higher free surface area. 

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