Lipids, cationic hydration

Neutral lonophores. The relationship between equilibrium ionophore affinities and dynamic biological transmembrane transport is detailed in Figure 2. The transport cycle catalyzed by neutral ionophores is given on the left. Ionophore added to a biological membrane partitions predominately into the membrane. A portion of the ionophore diffuses to the membrane Interface where it encounters a hydrated cation. A loose encounter complex is formed followed by replacement of the cationic hydration sphere by engulfment of the cation by the ionophore. The dehydrated complex is lipid-soluble and hence can diffuse across the membrane. The cation is then rehydrated, released, and the uncomplexed lono-phore freed to return to its initial state within the membrane. 

C. Hydrated monovalent cation approaching an area of the membrane where an amphiphilic carrier is located with its lipid side in contact with the lipid layer and with polar oxygens directed outward into solution. On close approach to the carrier, water molecules in the first coordination shell become replaced by carrier oxygens. As the ion becomes enclosed, the carrier moves into the lipid layer. 

Liposomes — These are synthetic lipid vesicles consisting of one or more phospholipid bilayers they resemble cell membranes and can incorporate various active molecules. Liposomes are spherical, range in size from 0.1 to 500 pm, and are thermodynamically unstable. They are built from hydrated thin lipid films that become fluid and form spontaneously multilameUar vesicles (MLVs). Using soni-cation, freeze-thaw cycles, or mechanical energy (extrusion), MLVs are converted to small unilamellar vesicles (SUVs) with diameters in the range of 15 to 50 nm. ... 

Bennett, M.J., Aberle A.M., Balasubramaniam R.P., Malone, J.G., Malone, R.W., and Nantz, M.H., Cationic lipid-mediated gene delivery to murine lung correlation of lipid hydration with in vivo transfection activity, Journal of Medicinal Chemistry, 1997, 40, 4069 1078. 

As for conventional liposomes, temperature and time of incubation are important factors for PEG-lipid insertion into cationic bilayers (48). Transition temperature of cationic lipids has not always been determined, although it would be interesting data to have. The incorporation of PEG-lipid into the film before hydration is usually more efficient than its postinsertion into the particles. However, postincorporation allows to work with limited amounts of materials, and to test more easily multiple conditions. 

Biological membranes present a barrier to the free transport of cations, as the hydrophilic, hydrated cations cannot cross the central hydrophobic region of the membrane which is formed by the hydrocarbon tails of the lipids in the bilayer. Specific mechanisms thus have to be provided for the transport of cations, which therefore allow for the introduction of controls. Such translocation processes may involve the active transport of cations against the concentration gradient with expenditure of energy via the hydrolysis of ATP. These ion pumps involve enzyme activity. Alternatively, facilitated diffusion may occur in which the cation is assisted to cross the hydrophobic barrier. Such diffusion will follow the concentration gradient until concentrations either side of... 

In summary, our findings suggest that cholesterol and certain analogs are a highly valuable neutral lipid component ( helper lipid ) for CL-DNA complexes because they facilitate endosomal escape by reducing the repulsive hydration and protrusion forces. They are thus able to lower the kinetic barrier for fusion of the cationic membranes of CL-DNA complexes with the anionic membrane of the endosome and increase TE, in addition to their beneficial effect on aM. 

Consider a hydrophobic sensitizer such as tetramethylbenzidine145) or phenothiazine146 incorporated into an anionic micelle. After excitation these molecules will eject electrons via a tunnelling mechanism147,148) from the lipid into the aqueous phase where formation of hydrated electrons (e q) occurs. The sensitizer cation will remain within the micellar aggregate. 

The unique ability of hydrogen ions to move along hydrogen-bonded chains suggested a possible flux mechanism that would differentiate between the permeation of protons and other cations. Perhaps ions do not dissolve in the bilayer to cross the membrane. Instead, transient hydrated defects may be produced by thermal fluctuations in the lipid, and ions could then cross the membrane barrier by diffusion through the defects. If water molecules in the defects are associated by hydrogen bonding, protons could cross the... 

The dimensions of the interior cavity nicely accommodate a K+ ion but do not fit other cations as well. This structure is exactly what is needed for a cation carrier The outer surface is hydrophobic, making the molecule soluble in the lipid bilayer, whereas the inside mimics in some ways the hydration shell that the cation would have in aqueous solution. A molecule like valinomycin can diffuse to one surface of a membrane, pick up an ion, and then diffuse to the other surface and release it. There is no directed flow, but the carrier, in effect, increases the solubility of the ion in the membrane. 

For examfde, cyclic dodecadepsipeptide antibiotic valinomycin (18) is represented as Cyclo D-Val-Lac-Val-D-ifyv)3 where Lac and Hyv re esent lactic acid and a-oxyisobutyric add, re ctively. ValinoiiQrcin selectively binds K, when it acts as an antibiotic. As shown in Fig. 31, valinomycin takes a bracelet structure and has a cavity in the middle with a diameter of 6—7A. Sizes of hydrated cations are 4.5—5.0 A for K, Rb, and Cs and 5.5—7.4 A for Na and Li . It is understandable that the cavity fits in with K. Carbonyl groups are distributed along the inside wall of the cavity which is necessarily polar. Alifdiatic side chains form the outside wall of the bracelet whidi is necessarily nonpolar. Valinomycin binds in the hydro-0ulic interior of the cavity and transports the ion across the lipid bilayer of the cell... 

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