Bilayers, permeability

Joguparthi, V, Xiang, T.-X. and Anderson, B.D. (2007) Liposome transport of hydrophobic drugs gel phase lipid bilayer permeability and partitioning of the lactone form of a hydrophobic camptothecin, DB-67. Journal of Pharmaceutical Sciences, 97, 400-420. 

Walde, P. and Mazzetta, B. (1998) Bilayer permeability-based substrate selectivity of an enzyme in liposomes. Biotechnol Bioeng., 57,216-19. 

The permeability of solutes across lipid bilayers is a product of the partition coefficient and the transverse diffusion coefficient [30]. Bilayer polymerization can alter solute diffusion by modifying either or both of these processes. In order to examine the effect of polymerization on bilayer permeability a nonionic solute of moderate permeability, [3H-glucose], was encapsulated in the vesicles prior to polymerization, removed from the exterior after polymerization, and its permeation across the bilayer was measured periodically [31]. Quantitative measurements of the 3H-glucose leakage revealed that the formation of linear polymer chains from methacryloyl lipids reduced the permeability coefficient to 0.3 to 0.5 of that of the unpolymerized lipid vesicles. A larger reduction (two orders of magnitude) was only found when crosslinked polymer networks were formed [31]. 

Release of liposome-encapsulated CF from HA/PLL films has been observed at temperatures above the lipid transition temperature (Fig. 4f). Below this temperature, the vesicles were stable at least for a few hours. The polyelectrolyte network destabilizes the embedded vesicles, which show higher lipidic bilayer permeability upon heating than do vesicles in solution [84], No change in film properties upon heating has been reported as proof of the polyelectrolyte destabilization effect. 

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. 

In bacteria, a family of molecules with a striking chemical similarity to cholesterol, the hopanoids, insert into the membrane hemilayer and stabilize membrane structure (figure 7.28 bacteriohopanetetrol). The effects of these prokaryotic cholesterol analogs are similar to those of cholesterol they broaden the gel-fluid phase transition, condense the bilayer, and reduce bilayer permeability. Contents of hopanoids in bacterial membranes may rise with acclimation temperature (Poralla et ah, 1984). 

Urquhart R, Chan RY, Li OT, TiUey L, Grieser F, Sawyer WH. Omega-6 and omega-3 fatty acids monolayer packing and effects on bilayer permeability and cholesterol exchange. Biochem Int 1992 26 831-841. 

Gerasimov, O.V., Schwan, A., and Thompson, D.H. (1997) Acid-catalyzed plasmenylcholine hydrolysis and its effect on bilayer permeability a quantitative study, Biochim. Biophys. Acta, 1324, 200-214. 

The influence of plant sterols on the phase properties of phospholipid bilayers has been studied by differential scanning calorimetry and X-ray diffraction [206]. It is interesting that the phase transition of dipalmitoylglycerophosphocholine was eliminated by plant sterols at a concentration of about 33 mole%, as found for cholesterol in animal cell membranes. However, less effective modulation of lipid bilayer permeability by plant sterols as compared with cholesterol has been reported. The molecular evolution of biomembranes has received some consideration [207-209]. In his speculation on the evolution of sterols, Bloch [207] has suggested that in the prebiotic atmosphere chemical evolution of the sterol pathway if it did indeed occur, must have stopped at the stage of squalene because of lack of molecular oxygen, an obligatory electron acceptor in the biosynthetic pathway of sterols . Thus, cholesterol is absent from anaerobic bacteria (procaryotes). 

Lipids have multiple functions in cells ranging from defining the bilayer permeability barrier of cell membranes and organelles to providing the matrix within which membrane proteins fold and function to being integral components of... 

Another method relies on thermal properties of lipid membranes. Every lipid bilayer is characterized by a phase transition, from solid-like to liquid-like states. It is known that at the transition temperature (called melting temperature, r ), the bilayer permeability is maximal. It is then possible to exploit this higher permeability to allow solutes pass through the membrane (Figure 17.5.4). It has been reported, for example, that ATP permeability increase by a factor -100 in dimyristoyl phosphatidylcholine vesicles, and that such vesicles can therefore be fed with ATP by keeping them at the (23.3 °C). It... 

Urel, however, encodes an inner membrane protein with six transmembrane segments and is likely to be the transporter that is acid activated, enabling urea access to intrabacterial urease. Hence, in the absence of activation of this urea transporter, urea has slow, bilayer permeability-determined access to the urease, and there is low activity of the urease above pH 6.5. With activation, there is a large increase in urea entry and, thus, increase in intrabacterial urease. 

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,... 

The failure of correlations led to a consideration of possible unique features of the bilayer as corrections. Lieb and Stein proposed that the bilayer permeability has features in common with the permeation of soft polymers by gases. This suggests that molecular volume, in addition to solubility, might be a determinant of permeation. As suggested, correction for molecular size improved the correlations. Miller ... 

---