Bilayer interfaces

NMR Studies on Lipid Bilayer Interfaces Coupled with Anesthetics and Endocrine Disruptors... 

Molecular study of lipid bilayer interfaces is necessary for a better understanding of the membrane-drug interaction and DD into biomembranes. The points to be clarified are (1) How can we determine DD sites at the bilayer interface (2) What kind of method is advantageous (3) Is it possible to unambiguously specify the bilayer interfacial portion coupled with drugs (4) What are most important characteristics of DD at the bilayer interface In order to answer these important questions, this chapter has been planned. We will emphasize the significance of the molecular level information obtainable from NMR studies. 

IV. LIPID BILAYER INTERFACES COUPLED WITH ANESTHETICS... 

General anesthetics are usually small solutes with relatively simple molecular structure. As overviewed before, Meyer and Overton have proposed that the potency of general anesthetics correlates with their solubility in organic solvents (the Meyer-Overton theory) almost a century ago. On the other hand, local anesthetics widely used are positively charged amphiphiles in solution and reversibly block the nerve conduction. We expect that the partition of both general and local anesthetics into lipid bilayer membranes plays a key role in controlling the anesthetic potency. Bilayer interfaces are crucial for the delivery of the anesthetics. 

We have shown that the cationic species are almost dominant and only a small portion of the cationic species is neutralized (discharged) when they are trapped at the bilayer interface. The discharging of the small portion of the cationic species DEC H in membranes is confirmed by the pH change study [48]. The proton should be released into the aqueous phase in the discharging process of DEC H+ at the membrane surface. In fact, the pH of the solution is decreased to a small extent after the addition of the EPC SUV. This means that only a small portion of the DEC H molecules is discharged the pH value is not decreased to the value of the complete discharging. The fraction of the DEC neutralized at the bilayer surface is estimated to be smaller than 1% of the total amount. 

Figures 14(a)-(d) represent the NMR spectral changes of the respective carbon atom sites of the EPC SUV caused by the BPA delivery at a low EPC concentration (12 mM) [47]. BPA induces the most prominent changes at the EPC carbon atom sites of the carbonyl (a), olefinic =CHCH9CH= (b), glycerol CH and CH2 (c), and chain P-CRi adjacent to the interface (d). These carbon atom sites are in good agreement with those specified by the H NMR. Thus these results provide complementary evidence that BPA is preferentially trapped in the bilayer interface.

Basic concepts and the methods for determining DD sites in lipid bilayer membranes have been developed by NMR on the atomic site level. Lipid bilayer interfaces as delivery sites can be specified by taking advantage of the site selectivity of NMR. DD sites can be generally classified into the three categories in Fig. 6. The distinction is based on the difference in the micropolarity in membranes around the drug. It has been briefly mentioned how to evaluate dynamic properties of drugs in membranes. 

Jacobs RE, SH White. (1989). The nature of hydrophobic binding of small peptides at the bilayer interface Implications for the insertion of transbilayer helices. Biochemistry 28 3421-3437. 

Fig. 5.22 (A-D) Scheme of Au nanoparticle growth between bilayers (A) nucleation at bilayer interfaces and bulk-like growth when particle size is smaller than the lamellar d spacing (B) once the transversal particle size is larger than the d spacing, growth is slowed by the bilayers, the transversal Au3+flux being limited, leadingto elongated particles shapes (C) when the constraint exerted by the particles on the bilayers is...

Find the steady-state concentration profile during the radial diffusion of a diffusant through a bilayer cylindrical shell of inner radius, Rm, where each layer has thickness AR/2 and the constant diffusivities in the inner and outer layers are Dm and Dout. The boundary conditions are c(r = Rln) = cin and c(r = Rm + Ai ) = cout. Will the total diffusion current through the cylinder be the same if the materials that make up the inner and outer shells are exchanged Assume that the concentration of the diffusant is the same in the inner and outer layers at the bilayer interface. 

Solution. The concentration profile at the bilayer interface will not have continuous derivatives. Break the problem into separate diffusion problems in each layer and then impose the continuity of flux at the interface. Let the concentration at the bilayer interface be c /°. 

Quesnel S, Silvius JR. Cysteine-containing peptide sequences exhibit facile uncatalyzed transacylation and acyl-coa-dependent acylation at the lipid bilayer interface. Biochemistry 1994 33 13340-13348. 

Model calculations of interface-solute electrostatic interactions reproduce well the view of microenvironment polarities of micelles and bilayers obtained from experimental data [57]. According to molecular dynamics simulations, at 1.2 nm from a bilayer interface, water has the properties of bulk water. At shorter distances, water movement slows as individual water molecules become attracted to the interface. At the true interface, which is a region containing both H2O molecules and the surfactant polar head groups, the water molecules are oriented with... 

Ultrasound exposure in the therapeutic range causes cavitation in the keratinocytes of the stratum corneum. Oscillations of the ultrasound-induced cavitation bubbles near the keratinocyte-lipid bilayer interfaces may, in turn, cause oscillations in the lipid bilayers, thereby causing structural disorder of the SC lipids (Fig. 4). Shock waves generated by the collapse of cavitation bubbles at the interfaces may also contribute to the structure-disordering effect. 

Figme 4.5 Local view of the hydrophilic-hydrophobic interfaces (parallel surfaces) and surfactant pacidng for a bilayer interface. If bodt monolayers are identically constituted, the mid-surface of the bilayer (at the free chain-ends) is a minimal surface. (For an interface consisting of a reversed bilayer the surfactant molecules are inverted so that the head groups lie closest to the mid-surface, and the volume between the minimal surface and the two parallel surfaces contains the polar matter, i.e. water and surfactant head-groups.)... 

Jain, M. K., Ranadive, G., Yu, B.-Z., and Verheij, H. M. (1991). Interfacial catalysis by phospholipase A2 Monomeric enzyme is fully catalytically active at the bilayer interface. Biochemistry 30,7330—7340. 

Ramirez, F., and Jain, M. H. (1991). Phospholipase As at the bilayer interface. Proteins Struct. Funct. Genet. 9, 229-239. 

The properties of the prewaves are reminiscent of the bilayer interfaces described below. Because of the similarities, their origins may lie in a chemical decomposition process which leads to two different types of spatially separated sites in the films. Alternatively, the prewaves may have a non-Faradaic, structural origin in which changes occur as a consequence of the gain or loss of counterions in the films upon oxidation or reduction. 

Between the bilayer and solution experiments it is possible to begin to show how to transfer the rectifying properties observed on photolysis at a semiconductor-solution interface to any electrode material. In a more general context, it seems clear that the single layer and bilayer interfaces have intrinsic characteristics usually associated with solid state electronics devices. 

Jacobs RE and White SH. The Nature of Hydrophobic Binding of Small Peptides at the Bilayer Interface Implications for the Insertion of Transbilayer Helices. Biochemistry 1989 28 3421-3437. 

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