Phospholipids bilayer permeability

In both Navanax neurons (65) and an artificial phospholipid bilayer membrane (66). salicylic acid (1-30 mM) increased K" " permeability but decreased Cl- permeability resulting in a net Increase in membrane conductance. To account for the selective effect of salicylic acid (and other benzoic acids) on the two permeabilities, it was proposed that the anions of the organic acids adsorb to membranes to produce either a negative surface potential (66) or an increase in the anionic field strength of the membrane (47, 48). 

In the transport across a phospholipid bilayer by passive diffusion, the permeability of the neutral form of a molecule is 10X times greater than that of the charged form. For the epithelium, the discrimination factor is 105. The basement membrane (Fig. 2.5) allows passage of uncharged molecules more readily than charged species by a factor of 10 [76]. 

Figure 7.22b shows that hydrophilic molecules, those with log Kj < 1, are much more permeable in octanol than in olive oil. The same may be said in comparison to 2% DOPC and dodecane. Octanol appears to enhance the permeability of hydrophilic molecules, compared to that of DOPC, dodecane, and olive oil. This is dramatically evident in Fig. 7.7, and is confirmed in Figs. 7.8c and 7.22b. The mechanism is not precisely known, but it is reasonable to suspect a shuttle service may be provided by the water clusters in octanol-based PAMPA (perhaps like an inverted micelle equivalent of endocytosis). Thus, it appears that charged molecules can be substantially permeable in the octanol PAMPA. However, do charged molecules permeate phospholipid bilayers to any appreciable extent We will return to this question later, and will cite evidence at least for a partial answer. 

To reach such a site, a molecule must permeate through many road blocks formed by cell membranes. These are composed of phospholipid bilayers - oily barriers that greatly attenuate the passage of charged or highly polar molecules. Often, cultured cells, such as Caco-2 or Madin-Darby canine kidney (MDCK) cells [1-4], are used for this purpose, but the tests are costly. Other types of permeability measurements based on artificial membranes have been considered, the aim being to improve efficiency and lowering costs. One such approach, PAMPA, has been described by Kansy et al. [5],... 

Dr. Thomas drew our attention to the fact that, although biological membranes are thin in comparison to his preparations, their diffusion constants may be long. I have measured permeability coefficients (transmembrane "diffusion ) for a number of solutes for artificial phospholipid bilayers (liposomes). The values follow and are to be compared for calculated permeabilities for a solute diffusion across a comparable thickness of water. 

Cell membrane The phospholipid bilayer that surrounds a cell, forming a selectively-permeable barrier. 

Action on the membrane components Numerous studies have shown that the passive transcellular transport of hydrophilic compounds, including macromolecules such as peptides, can be enhanced by interaction of the penetration enhancers with both the phospholipid bilayer and the integrated proteins, thereby making the membrane more fluid and thus more permeable to both lipophilic and hydrophilic compounds. 

We can now consider some typical nutrient solutes like amino acids and phosphate. Such molecules are ionized, which means that they would not readily cross the permeability barrier of a lipid bilayer. Permeability coefficients of liposome membranes to phosphate and amino acids have been determined [46] and were found to be in the range of 10 11 -10 12 cm/s, similar to ionic solutes such as sodium and chloride ions. From these figures one can estimate that if a primitive microorganism depended on passive transport of phosphate across a lipid bilayer composed of a typical phospholipid, it would require several years to accumulate phosphate sufficient to double its DNA content or pass through one cell cycle. In contrast, a modern bacterial cell can reproduce in as short a time as 20 min. 

How does this shift from fluid to gel state during desiccation cause damage to the membrane, and how does the presence of trehalose or sucrose—water substitutes—prevent this damage As the anecdote about baking technique implies, the crux of the problem occurs when dried cells are rehydrated. It is known from studies of model membranes that when phospholipid bilayers pass through the temperature range over which the gel phase is replaced by the liquid crystalline phase, transient changes in membrane permeability occur (Crowe et al., 1997). The precise mechanism responsible for this transient breakdown in the permeability barrier is not entirely clear, but it... 

Vesicles made by the methods described in the preceding questions are virtually impermeable to small cations and to most large polar molecules. They are slightly permeable to Cl, and the permeability of water is high because the solubility of water in liquid hydrocarbon is significant. When proteins are present during vesicle formation, they may be incorporated into the phospholipid bilayer. Such vesicles are known as proteoliposomes. 

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