Permeability, phospholipid monolayers

Kimelberg and Papahadjopoulos (7) assume that the hydrophobic areas of bound proteins can deform the phospholipid monolayer, compelling the fatty acyl liquid chains of the monolayer molecules to orientate parallel to the surface. They conclude that this effect may control the permeability of membranes, but they do not discuss how this reorientation of the acyl chains can produce positive values of All. The reorientation term of Equation 8 explains the origin of this increase in An since this term is positive when H > ai°. 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

Fig. 21). The negatively charged DLPE monolayer accelerates the transfer of the former ion and reduces appreciably the transfer of the latter ion. The effect is reversed in the case of a positively charged DLPE monolayer. The authors concluded that the ion permeability is primarily determined by the hydrodynamic friction and the double layer effect arising from the sign and density of the surface charge of adsorbed phospholipid molecules. 

Studies of the physical properties of UC, reviewed in Chapter 6 of this volume, have contributed much to our understanding of the role of this Upid in membranes and lipoprotein surfaces. The shape and polarity of UC promote its association with the phosphoUpids of membranes and Upoproteins, and this association has important effects on membrane fluidity and permeability. The physical properties of long-chain fatty acid esters of cholesterol, on the other hand, differ strikingly from those of UC, and cause these esters to be largely excluded from phospholipid bilayers and monolayers and to aggregate instead in oil droplets. 

Efforts to stabilize BLMs by the use of polymerizable lipids have been successful, but the electrochemical properties of these membranes were greatly compromised and ion channel phenomena could not be observed [21]. Microfiltration and polycarbonate filters, polyimide mesh, and hydrated gels have been used successfully as stabilizing supports for the formation of black lipid films [22-25] and these systems were observed to retain their electrical and permeability characteristics [24]. Poly(octadec-l-ene-maleic anhydride) (PA-18) was found to be an excellent intermediate layer for interfacing phospholipids onto solid substrates, and is sufficiently hydrophilic to retain water for unimpeded ion transfer at the electrode-PA-18 interface [26]. Hydrostatic stabilization of solventless BLMs has been achieved by the transfer of two lipid monolayers onto the aperture of a closed cell compartment however, the use of a system for automatic digital control of the transmembrane pressure difference was necessary [27]. 

The cell membrane is an absolute necessity for life because by it the cell can control its interior by controlling the membrane permeability. If the membrane is destroyed, then the cell dies. The membrane is a layer that separates two solutions and forms two sharp boundaries toward them. The cell membrane consists of phospholipids that form a bilayer lipid membrane (BLM) approximately 7 nm thick (Figure 4.6). Each monolayer has its hydrophobic surface oriented inward and its hydrophilic surface outward toward the intracellular or extracellular fluids. The inside of such a bilayer is hydrophobic and lipophilic. A BLM is a very low electric conductivity membrane and is accordingly in itself closed for ions. It lets lipids pass but not water. However, water molecules can pass specialized membrane channels (cf. Chapter 5). The intrinsic conductance is on the order of 10 S/m, and a possible lipophilic ionic conductivity contribution cannot be excluded. 

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