Biomembrane composition

Although the drug delivery to the lipid bilayer membrane is just the first step for bioactivities and phopholipid vesicles are rather simple in view of the composite structure of biomembranes, the unambiguous specification of the preferential location of the drug is essential the successive processes of the action are expected to be induced via the delivery site in membranes. We expect more advances in the dynamic NMR study, so that we can get insight into the mechanism of DD in membranes. 

Y.J. Hu, N.F. Hu, and Y.H. Zeng, Electrochemistry and electrocatalysis with myoglobin in biomembrane-like surfactant-polymer 2C 2N+PA composite films. Talanta 50, 1183-1195 (2000). 

Abstract To understand how membrane-active peptides (MAPs) function in vivo, it is essential to obtain structural information about them in their membrane-bound state. Most biophysical approaches rely on the use of bilayers prepared from synthetic phospholipids, i.e. artificial model membranes. A particularly successful structural method is solid-state NMR, which makes use of macroscopically oriented lipid bilayers to study selectively isotope-labelled peptides. Native biomembranes, however, have a far more complex lipid composition and a significant non-lipidic content (protein and carbohydrate). Model membranes, therefore, are not really adequate to address questions concerning for example the selectivity of these membranolytic peptides against prokaryotic vs eukaryotic cells, their varying activities against different bacterial strains, or other related biological issues. 

Given the overwhelming compositional complexity of biomembranes, a slightly better representation can be achieved when lipid extracts from native sources are used... 

Koynova R, MacDonald RC (2007) Natural lipid extracts and biomembrane-mimicking lipid compositions are disposed to form nonlamellar phases, and they release DNA from lipoplexes most efficiently. Biochim Biophys Acta-Biomembranes 1768 2373-2382... 

The influence of lipid phase (gel or liquid crystalline), cholesterol content, lipid composition (egg phosphatidylcholine or DPPC), and structure of benzodiazepines determine their localization in the membrane. The strength of benzodiazepine-membrane interaction increases with a decrease in molecular order, molecular packing, and hydration,. The authors point to the pharmacological relevance of theses results because the extent of partitioning of these drags into biomembranes would be coupled to local oscillation of membrane dynamics which may be induced by physiological events. ... 

Most biomembranes are in the liquid crystalline phase under physiological conditions and their complex composition makes it more difficult to measure phase transitions. It should be mentioned that the effect of drug molecules on fluidity and order of a membrane can even be reversed below and above Tt [169] and NMR measurements of drug-membrane interactions are normally performed above Tt. 

Several classes of lipids common for the biomembranes can form inverted nonlamellar phases under physiologic conditions (4). The principle ones are phosphatidylethanolamines and monogalactosyldiglycerides. Also, cardiolipins and phos-phatidic acids can form inverted phases in the presence of divalent cations, and phosphatidylserines and phosphatidic acids both form inverted phases at low pH. Moreover, biomembrane lipid extracts and membrane-mimicking lipid compositions form nonlamellar phases if heated above physiologic temperatures, dehydrated, or treated with divalent cations (5-7). 

Compared with lAM, which uses a monolayer of phospholipid, the liposomal phospholipid bilayers in ILC have the advantage of closely resembling biologic membrane bilayers and constitute a 2-D fluid in which lipid molecules and other components are free to diffuse (10). With this technique, the phospholipid composition can be changed to mimic the membrane of interest. Membrane lipids extracted from human cells also can be used the technique then is called immobilized biomembrane chromatography (IBC) (11). 

The composition of lipids varies markedly in a cell, and biomembranes and lipoproteins provide crisp examples about the diversity of different lipids. 

In this study, the TC-CCC system was applied to solve the problem of emulsification, and satisfactory stationary phase retention was obtained. Human brain lipids could then be separated. We established the solvent systems that are used for the separation of most of the phospholipids, glycolipids, and less-polar hpids of the human brain. Furthermore, we demonstrated that molecular species, which are derived from variations of the hydrophobic tail group, were separated by optimizing the composition of the solvents. TC-CCC is available for analyzing the hydrophobicities of various lipid molecules in biomembranes. 

Gruner SM. Intrinsic curvature hypothesis for biomembrane lipid composition a role for nonbilayer lipids. Proc Natl Acad Sci USA 1985 82 3665-3669. 

Phospholipids of the composition present in cells spontaneously form sheetlike phospholipid hilayers, which are two molecules thick. The hydrocarbon chains of the phospholipids in each layer, or leaflet, form a hydrophobic core that is 3-4 nm thick in most biomembranes. Electron microscopy of thin membrane sections stained with osmium tetroxide, which binds strongly to the polar head groups of phospholipids, reveals the bilayer structure (Figure 5-2). A cross section of all single membranes stained with osmium tetroxide looks like a railroad track two thin dark lines (the stain-head group complexes) with a uniform light space of about 2 nm (the hydrophobic tails) between them. 

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