Membrane charged lipids

FIGURE 6-15 Schematic representation of the ion permeability modulation for cation-responsive voltammetric sensors based on negatively charged lipid membranes. Complexation of the guest cation to the phospholipid receptors causes an increase of the permeability for the anionic marker ion. (Reproduced with permission from reference 49.)... 

Tables 7.6-7.8 list the Pe, SD, and %R of the 32 probe molecules in the thirteen new PAMPA lipid models, one of which is 2% DOPC assayed under sink conditions (model 1.1). The latter model served as a benchmark for assessing the effects of negative membrane charge.

The negative-charge lipid content in the egg lecithins is not as high as that found in BBM and especially BBB lipids (Table 7.1). Furthermore, the negative-charge content in the egg lecithin is about one-fourth that in the soy lecithin. This is clearly evident in the membrane retention parameters for the bases at the 10% lecithin levels (models 12.0 or 14.0 in Table 7.8 vs. model 16.0 in Table 7.12), as they are 20-30% lower for the lipophilic bases in egg, compared to soy. 

Figure 3.6 compares iso-pH permeabilities of ketoprofen at various pH values in a 2% DOPC-dodecane model (open circles) and the 20% soy lecithin with SLS in the acceptor compartment (filled circles, data in Table 3.5). In the presence of the latter negatively charged lipids (with the make-up similar to that of BBM in Table 3.1), ketoprofen is intrinsically more permeable, by a factor of 17. The UWL limit, indicated by the solid curves in low-pH solutions, and consistent with the permeability Pu 19.8 x 10-6 cm s 1 (log Pu —4.7), masks the true intrinsic permeability of the membranes, P0. However, it is possible to deduce the membrane permeability if the pKa is known. In Fig. 3.6, the bending in the dashed (calculated) curves at pH 4 corresponds to the pKa of the molecule. Due to the UWL, the point of bending is shifted to higher pH values in the solid (measured) curves. The difference between the apparent pKa (pK 5.3 for DOPC and 6.3 for soy) and the true pKa (4.12) is the same as the difference between log P0 and log Pu [23],... 

The organization of lipids around the plasma membrane Ca2+-transport ATPase of erythrocytes has been also determined by FRET. Taking advantage of the intrinsic fluorescence of the ATPase due to tryptophan residues and labeling different types of lipids with pyrene, it was demonstrated that the transporter is preferentially surrounded by negatively charged lipids such as phosphoinositides [167],... 

If charged lipids are incorporated in the membrane phase (indicated by subscript m) or if charged species are sorbed to the membrane surface, an electrochemical potential jlim will build up according to ... 

Figure 7. Lipophilicity profile of propranolol in liposomes composed of zwitterionic and charged lipids (phosphatidyl ethanolamine (PE), oleic acid (OA), phosphatidyl inositol (PI)). Conditions of measurements are described in [113]. The dotted line indicates the partitioning profile of propranolol in the egg PC liposome system. The bars show the pH-dependent charge profile of propranolol (hatched bars positively charged propranolol) and the lipids in the membrane (black bars negatively charged lipids). Reprinted from [113] Kramer, S. (2001). Liposome/water partitioning , In Pharmacokinetic Optimization in Drug Research, eds. Testa, B. et al. Reproduced by permission of Verlag Helvetica Chimica Acta, Zurich...

At some point, these kinetic results for insulin on a biological membrane should be compared to kinetic results for insulin on an artificial lipid membrane, when such results become available. This comparison should be especially interesting in view of the suggestion by Sui et a/.(124) that nonspecific equilibrium binding of insulin to planar membranes is a function not only of membrane charge but also of some sort of nonelectrostatic mechanism, based on their TIRF experiments with a chamber adapted to a standard spectro-fluorimeter chamber. 

Tsui, F.C., Sundberg, S.A. and Hubbell, W.L., 1990, Distribution of charge on photoreceptor disc membranes and implications for charged lipid asymmetry. Biophys. J. 57 85-97. 

Early investigations of peptides in membrane model systems included studies of mel-letin 124,125 220 221 spectra and polarization properties. This water-soluble peptide is found to be structureless in solution at neutral pH but was sensitive to environmental change. The undecapeptide hormone, substance P, a member of the tackykinin family, was also found by Choo et a].1222 to be unstructured in solution at physiological pH and to aggregate at high pH or on interaction with charged lipids. These data were used as counter-evidence to a hypothesis that the membrane surface structured the peptide to facilitate interaction with the receptor. 

Figure 10.4 (A) The DNA interaxial distance dDNA and the interlayer distance d in the L°a phase (Figure 10.2) plotted as a function of Lipid/DNA (UD) (wt/wt) ratio at the isoelectric point of the0 complex DOTAP/DNA=2.2. dDNA is seen to expand from 24.5 A to 57.1 A. The solid line through the data is the prediction of a packing calculation where the DNA chains form a space rilling one-dimensional lattice. (B) Schematic drawing of DNA-membrane multilayers showing the increase in distance between DNA chains as the membrane charge density is decreased (i.e., as DOpc increases) at the isoelectric point (Adapted from Raedler et al., 1997 Kohover etal., 1999).

Lin AJ, Slack NL, Ahmad A et al (2003) Three-dimensional imaging of lipid gene-carriers membrane charge density controls universal transfection behavior in lamellar cationic liposome-DNA complexes. Biophys J 84 3307-3316... 

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