Membrane lipid bilayers water permeability

In special cases (as in colloidal solutions) some particles can be considered as essential and other particles as irrelevant , but in most cases the essential space will itself consist of collective degrees of freedom. A reaction coordinate for a chemical reaction is an example where not a particle, but some function of the distance between atoms is considered. In a simulation of the permeability of a lipid bilayer membrane for water [132] the reaction coordinate was taken as the distance, in the direction perpendicular to the bilayer, between the center of mass of a water molecule and the center of mass of the rest of the system. In proteins (see below) a few collective degrees of freedom involving all atoms of the molecule, describe almost all the... 

Figure 41-6. Permeability coefficients of water, some ions, and other small molecules in lipid bilayer membranes. Molecules that move rapidly through a given membrane are said to have a high permeability coefficient. (Slightly modified and reproduced, with permission, from Stryer L Biochemistry, 2nd ed. Freeman, 1981.)...

It has been known for some years that gramicidin forms transmembrane ion channels in lipid bilayers and biological membranes and that these channels are assembled from two molecules of the polypeptide 213). The channels are permeable specifically to small monovalent cations [such as H+, Na+, K+, Rb+, Cs+, Tl+, NH4+, CHjNHj, but not (CH3)2NH2+J and small neutral molecules (such as water, but not urea). They do not allow passage of anions or multivalent cations 21 n. 

In series with a desolvation energy barrier required to disrupt aqueous solute hydrogen bonds [14], the lipid bilayer offers a practically impermeable barrier to hydrophilic solutes. It follows that significant transepithelial transport of water-soluble molecules must be conducted paracellularly or mediated by solute translocation via specific integral membrane proteins (Fig. 6). Transcellular permeability of lipophilic solutes depends on their solubility in GI membrane lipids relative to their aqueous solubility. This lumped parameter, membrane permeability,... 

The lipid bilayer arrangement of the plasma membrane renders it selectively permeable. Uncharged or nonpolar molecules, such as oxygen, carbon dioxide, and fatty acids, are lipid soluble and may permeate through the membrane quite readily. Charged or polar molecules, such as glucose, proteins, and ions, are water soluble and impermeable, unable to cross the membrane unassisted. These substances require protein channels or carrier molecules to enter or leave the cell. 

Passive diffusion through the lipid bilayer of the epithelium can be described using the partition coefficient between octanol/water (log P) and A log P (the difference between the partition into octanol/water and heptane/ethylene glycol or heptane/ octanol) [157, 158], The lipophilicity of the drug (log P) (or rather log D at a certain pH) can easily be either measured or calculated, and is therefore generally used as a predictor of drug permeability. Recently, a method using artificial membrane permeation (PAMPA) has also been found to describe the passive diffusion in a similar manner to the Caco-2 cell monolayers [159]. 

To move through the membrane (change sides or transverse diffusion), a molecule must be able to pass through the hydrophobic portion of the lipid bilayer. For ions and proteins, this means that they must lose their interactions with water (desolvation). Because this is extremely difficult, ions and proteins do not move through membranes by themselves. Small molecules such as C02, NH3 (but not NH ). and water can diffuse through membranes however, most other small molecules pass through the lipid bilayer very slowly, if at all. This permeability barrier means that cells must develop mechanisms to move molecules from one side of the membrane to the other. 

In the literature, one can find many more interesting MD studies concerning lipid bilayers with additives. In particular, a wealth of MD simulations of such systems is in the field of anaesthetics (for a review see [142]). Many anaesthetics tend to accumulate at the membrane/water interface, implying that their potencies are not related to their ability to cross the membrane. Instead, it seems to be more likely that their functioning is via binding to membrane receptors. Generally, they have an effect opposite to that of cholesterol, i.e. they increase the membrane fluidity and permeability. 

Osmosis, water movement across a semipermeable membrane driven by differences in osmotic pressure, is an important factor in the life of most cells. Plasma membranes are more permeable to water than to most other small molecules, ions, and macromolecules. This permeability is due partly to simple diffusion of water through the lipid bilayer and partly to protein channels (aquaporins see Fig. 11-XX) in the membrane that selectively permit the passage of water. Solutions of equal osmolarity are said to be isotonic. Surrounded by an isotonic solution, a cell neither gains nor loses water (Fig. 2-13). In a hypertonic solution, one with higher... 

The rate at which a drug molecule diffuses across the lipid bilayer of the cell membrane depends largely on the size of the molecule and its relative lipid solubility. In general the smaller and more hydrophobic the molecule, the more rapid will be its diffusion across the bilayer. However, cell membranes are also permeable to some small, water-soluble molecules such as ions, sugars, and amino acids [19]. 

The third class of lipids found in stratum corneum extracts is represented by cholesterol and cholesteryl esters. The actual role of cholesterol remains enigmatic, and no clear reason for its role in the barrier function has been proposed so far. However, it is possible that contrary to what is the role in cell membranes where cholesterol increases close packing of phospholipids, it can act as kind of a detergent in lipid bilayers of long-chain, saturated lipids.30,31 This would allow some fraction of the barrier to be in a liquid crystalline state, hence water permeable in spite of the fact that not only ceramides, but also fatty acids found in the barrier are saturated, long-chain species.28,32... 

Aquaporins (AQPs) are a family of at least 13 members of small membrane-spanning proteins that assemble in cell membranes as homotetramers (Verkman and Mitra, 2000 Agre et al 2002 Verkman, 2005). Each monomer is approximately 30 kDa and six a-helical domains with cytosolically oriented amino- and carboxy-termini surround the water pore (Verkman and Mitra, 2000). AQPs can transport water in both directions (Tail et al., 2008). Early experiments demonstrating that erythrocyte membranes are more permeable to water than expected from water diffusion through a lipid bilayer provided the first experimental evidence of the existence of AQPs (Sidel and Solomon, 1957). 

An obvious hypothesis is that this unusual membrane lipid composition is related directly to membrane function in some way. Within the restricted area of lipid bilayers, lipid composition is known to be an important determinant of physical properties. There are several prominent examples. First, the temperature at which the hydrocarbon chains melt when assembled in bilayers (the gel-to-liquid-crystalline transition temperature, marks an abrupt change in many of the physical properties of such bilayer systems for example, water permeability through such bilayers increases by several orders of magnitude above the transition. Second, the presence of cholesterol within bilayers composed of amphipathic lipids has a profound effect on lipid motion, mechanical properties (such as resistance to shear), and permeability to water. 

The distribution coefficient between a liposome phase (see above about the membrane phase) and a water phase also has been used instead of an octanol/water partition coefficient (log P). The liposome phase provides a biomimetic environment to a much larger degree compared with the octanol phase and has shown to the ability to predict in vivo permeability more precisely (13). Lipid bilayer-containing partition systems thus have been considered to model the hydrogen-bonding abU-... 

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... 

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