Penetration into bilayer lipid

Ras is strictly localized to the inner side of the plasma membrane. A lipid anchor covalently attached to the C-terminus of Ras penetrates into the lipid bilayer. This membrane anchorage is essential for the biological activity of Ras. Hence, the inhibition of anchor attachment has become an attractive pharmacological target [ 13]. See Waldmann H, Thutewohl M,Ras-Farnesyltransferase-inhibitors as promising anti-tumor drugs, this volume. 

As mentioned earlier, fullerene molecules can destroy the virions, but do not affect living cells. It is possible to suppose that the differences of the structures of virion envelope and cell membrane are the main reason for this phenomenon the outer side of virion envelope is enriched with protein molecules, whereas the outer side of cell membranes is more lipophylic. On the one hand, fullerene molecules can interact with proteins (Belgorodsky et al., 2006), and on the other hand, their penetration into a lipid bilayer does not destroy them (Ikeda et al., 2005 Piotrovsky, 2006). So it is not unlikely that the difference in the structure of outer side is the main driving force of the observed differences in the response of virions and cells in the presence of C60. 

From the data presented here several conclusions may be reached regarding the effect of cholesterol on lipid bilayers. It is shown that, even if the presence of cholesterol in bilayers serves to moderate temperature-induced changes, its ability to affect the location of solubilized molecules is highly temperature dependent We have also shown, in accord with previous work (11), that the presence of cholesterol in the gel phase results in a larger separation between the lipid polar groups and this in turn allows water to penetrate into the lipid hydrophobic core. 

We have also determined the delivery sites of alkylbenzenes by NMR. As already described in Section III.A, PrBe are deeply transported to the chain tail region in the bilayer core and the delivery site can be classified into category III [46]. Benzene, however, cannot deeply penetrate into the hydrophobic core, zone III, but is trapped preferentially at the interfacial site of the bilayer, zone II the delivery site can be classified into category II. Although benzene is generally considered to be hydrophobic, the delivery site of benzene determined by NMR is reasonable in the sense of the 7r-electrons with some affinity for the hydrophilic sites of the bilayer. Both drug and lipid sides of the H NMR spectra show that alkylbenzenes can deeply penetrate into the bilayer interior in the order PrBe > ethylbenzene > toluene > benzene, which is consistent with the sequence of the insolubility in water. 

Figure 3 A hydrophobic permeant must negotiate through a complex series of diffu-sional and thermodynamic barriers as it penetrates into a cell. The lipid and protein compositions and charge distribution of the inner and outer leaflets of the membrane lipid bilayer can play limiting roles, particularly at the tight junction. Depending upon the permeant s characteristics, it may remain within the plasma membrane or enter the cytoplasm, possibly in association with cytosolic proteins, and partition into cytoplasmic membranes.

To investigate the extent of water penetration into the hydrocarbon region of lipid bilayers, pyrene linked to a carboxylic group via a paraffinic chain (e.g. 1-pyrenehexadecanoic acid) is best suited (L Heureux and Fragata, 1987). 

A bilayer formed from complex lipids, largely glycerophospholipids, forms the core structure of biological membranes. This bilayer forms a barrier to penetration of exogenous molecules into the cellular interior. Proteins penetrate into or through this bilayer. 

In addition, some flavonoids can differentially interact with membrane polar surfaces or penetrate into the bilayer, depending on certain characteristics of the reaction milieu. This is the case of quercetin, a flavonoid that at acidic pH is deeply embedded into planar lipid bilayers [Movileanu et al., 2000], while at... 

Tezel and Mitragotri [66] describe a theoretical analysis of the interaction of cavitation bubbles with the stratum corneum lipid bilayers. Three modes were evaluated—shock-wave emission, microjet penetration into the stratum corneum, and impact of microjet on the... 

FIGURE 16.2 Three possible modes through which inertial cavitation may enhance SC permeability, (a) Spherical collapse near the SC surface emits shock waves, which can potentially disrupt the SC lipid bilayers, (b) Impact of an acoustic microjet on the SC surface. The microjet possessing a radius about one tenth of the maximum bubble diameter impacts the SC surface without penetrating into it. The impact pressure of the microjet may enhance SC permeability by disrupting SC lipid bilayers, (c) Microjets may physically penetrate into the SC and enhance the SC permeability. (From Mitragotri, S., and Kost J., Adv. Drug Deliv. Rev., 56, 589, 2004. With permission.)... 

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