Generalized stern models of the electric double layer considering the spatial variation of permittvity and finite size of ions in saturation regime

The interaction between a charged metal implant surface and a surrounding body fluid (electrolyte solution) leads to ion redistribution and thus to formation of an electrical double layer (EDL). The physical properties of the EDL contribute essentially to the formation of the complex implant-biosystem interface. Study of the EDL began in 1879 by Hermann von Helmholtz and still today remains a scientific challenge. The present mini review is focused on introducing the generalized Stern theory of an EDL, which takes into account the orientational ordering of water molecules. To ascertain the plausibility of the generalized Stern models described, we follow the classical model of Stern and introduce two Langevin models for spatial variation of the relative permittivity for point-like and finite sized ions. We attempt to uncover the subtle interplay between water ordering and finite sized ions and their impact on the electric potential near the charged implant surface. Two complementary effects appear to account for the spatial dependency of the relative permittivity near the charged implant surface — the dipole moment vectors of water molecules are predominantly oriented towards the surface and water molecules are depleted due to the accumulation of counterions. At the end the expressions for relative permittivity in both Langevin models were generalized by also taking into account the cavity and reaction field.     

Interaction of furosemide with lipid membranes

Summary The interaction of furosemide with different phospholipids was investigated. Its influence on the lipid structure was inferred from its effect on the phase transition properties of lipids and on the conductance of planar bilayer membranes. The thermotropic properties of dipalmitoyl phosphatidylcholine, phosphatidylethanolamine (natural), dipalmitoyl phosphatidylethanolamine, brain sphingomyelin, brain cerebrosides and phosphatidylserine in the presence and absence of furosemide were investigated by differential scanning calorimetry,. The modifying effect of furosemide seems to be strongest on phosphatidylethanolamine (natural) and sphingomyelin bilayers. The propensity of furosemide to decrease the electrical resistance of planar lipid membranes was also studied and it is shown that the drug facilitates the transport of ions. Partition coefficients of furosemide between lipid bilayers and water were measured.Abbreviations DSC differential scanning calorimetry - PLM planar lipid membranes - DPPC dipalmitoyl phosphatidylcholine - DMPC dimyristoyl phosphatidylcholine - PE phosphatidyl ethanol     

Molecular-dynamic simulation of DPPC bilayer in different phase state: Hydration and electric field distribution in the presence of Be<Superscript>2+</Superscript> cations

New molecular-dynamic topology of phosphatidylcholine bilayer (DPPC) in total atomic OPLS force field was developed and used to study the structural characteristics of liquid-crystalline and gel state of lipid bilayer in the absence and in the presence of Na⁺ and Be²⁺ cations adsorbed at the interface and different in their affinity. The parameters of bilayer geometry, the amount of surface water, and the electrostatic potential distribution were estimated quantitatively from the simulation in both phase states. The azimuthal angle of hydrocarbon chains was found nearly the same in the region of each monolayer in gel state. The amount of surface water decreases upon bilayer “freezing” mainly by loss of water molecules not participating in H-bonds between lipid headgroups. The cation adsorption was shown to have a small effect on these H-bonded water molecules, whereas Be²⁺ appeared to retain surface water in the bilayer upon its freezing. The electric potential distribution in the normal direction to the membrane-water interface had a similar shape in any bilayer phase state regardless of the presence of the adsorbed cations. Analysis of the microscopic nature of the electric potential revealed a mutual compensation of the contributions of the main structural components of the system (lipids, water, and ions). The boundary potential increased by 116 mV for pure DPPC, by 212 mV in the presence of Na⁺, and by 133 mV in the presence of Be²⁺ upon the phase transition of bilayer to the gel state. The boundary potential difference in the presence of Na⁺ and Be²⁺ and its change at the bilayer phase transition are in a good agreement with the experimental data published earlier [Ermakov Yu.A., 1993].     

Effect of 3-phenylindole on lipophilic ion and carrier-mediated ion transport across bilayer lipid membranes

The physical effects of 3-phenylindole, an antimicrobial compound which interacts with phospholipids, on ion transport across phosphatidylcholine-cholesterol bilayers have been investigated using three lipophilic ions and one ion-carrier complex. It was found that 3-phenylindole increased membrane electrical conductance of positively charged membrane probes and decreased electrical conductance of negatively charged probes. The enhancement of conductance detected by nonactin-K+ complex and tetraphenylarsonium+ was several orders of magnitude, whereas the suppression of conductance due to tetraphenylborate- and dipicrylamine- was less than a factor of ten. Presence of 3-phenylindole in aqueous phase slightly decreased adsorption of tetraphenylborate- and dipicrylamine- at the membrane surface. From the voltage dependence of the steady-state conductance it was shown that 3-phenylindole induced kinetic limitation of membrane transport of potassium mediated by nonactin. No such limitation was found in the case of tetraphenylarsonium+ transport. These results are shown to be consistent with the present concept of ion diffusion in membranes and the assumption that 3-phenylindole decreases the electric potential in the membrane interior. The asymmetry of the effect of 3-phenylindole on the magnitude of conductance changes for positively and negatively charged membrane permeable ions is also discussed as a reflection of the discreteness of both the absorbed 3-phenylindole and lipid dipoles.     

The effects of temperature,salinity, concentration and PEGylated lipid on the spontaneous nanostructures of bicellar mixtures

The self-assembling morphologies of low-concentration (mostly 1 and 10 mg/mL) bicellar mixtures composed of zwitterionic dipalmitoyl (di-C₁₆) phosphatidylcholine (DPPC), dihexanoyl (di-C₆) phosphatidylcholine (DHPC), and negatively charged dipalmitoyl (di-C₁₆) phosphatidylglycerol (DPPG) were investigated using small angle neutron scattering, dynamic light scattering and transmission electron microscopy. A polyethylene glycol conjugated (PEGylated) lipid, distearoyl phosphoethanolamine-[methoxy (polyethyleneglycol)-2000] (PEG2000-DSPE), was incorporated in the system at 5 mol% of the total lipid composition. The effects of several parameters on the spontaneous structures were studied, including temperature, lipid concentration, salinity, and PEG2000-DSPE. In general, nanodiscs (bicelles) were observed at low temperatures (below the melting temperature, T_M of DPPC) depending on the salinity of the solutions. Nanodisc-to-vesicle transition was found upon the elevation of temperature (above T_M) in the cases of low lipid concentration in the absence of PEG2000-DSPE or high salinity. Both addition of PEG2000-DSPE and high lipid concentration stabilize the nanodiscs, preventing the formation of multilamellar vesicles, while high salinity promotes vesiculation and the formation of aggregation. This study suggests that the stability of such nanodiscs is presumably controlled by the electrostatic interactions, the steric effect induced by PEG2000-DSPE, and the amount of DHPC located at the disc rim.     

Distance measurements using paramagnetic ion-induced relaxation in the saturation transfer electron spin resonance of spin-labeled biomolecules: Application to phospholipid bilayers and interdigitated gel phases

The saturation transfer electron spin resonance (STESR) spectra of spin-labeled phosphatidylcholines in gel phase lipid bilayers are shown to be sensitive to dipolar spin-spin interactions with paramagnetic ions in the aqueous phase. The reciprocal integrated intensity of the STESR spectrum is linearly dependent on aqueous Ni²⁺ ion concentration, hence, confirming the expectation that the STESR intensity is directly proportional to the spin-lattice relaxation time of the spin label. The gradient of the relaxation rate with respect to Ni²⁺ ion concentration decreases strongly with the position of the nitroxide group down the sn-2 chain of the spin-labeled lipid and is consistent with a 1/R³ dependence on the distance, R, from the bilayer surface. The values derived for the dimensions of the bilayer and lipid molecules in the case of dipalmitoyl phosphatidylcholine (DPPC) are in good agreement with those available from x-ray diffraction studies. Allowance for the multibilayer nature of the DPPC dispersions gives an estimate of the water layer thickness that is also consistent with results from x-ray diffraction. The profile of the paramagnetic ion-induced relaxation is drastically changed with DPPC dispersions in glycerol for which the lipid chains are known to be interdigitated in the gel phase. The terminal methyl groups of the lipid chains are located approximately in register with the C-3 atoms of the sn-2 chain of the oppositely oriented lipid molecules in the interdigitated phase. The thickness of the lipid layer and the effective thickness of the lipid polar group are reduced by ~40% in the interdigitated phase as compared with the bilayer phase. The calibrations of the distance dependence established by use of spin labels at defined chain positions should be applicable to STESR measurements on other biological systems.     

Spatial variation of permittivity of an electrolyte solution in contact with a charged metal surface: a mini review

Contact between a charged metal surface and an electrolyte implies a particular ion distribution near the charged surface, i.e. the electrical double layer. In this mini review, different mean-field models of relative (effective) permittivity are described within a simple lattice model, where the orientational ordering of water dipoles in the saturation regime is taken into account. The Langevin–Poisson–Boltzmann (LPB) model of spatial variation of the relative permittivity for point-like ions is described and compared to a more general Langevin–Bikerman (LB) model of spatial variation of permittivity for finite-sized ions. The Bikerman model and the Poisson–Boltzmann model are derived as limiting cases. It is shown that near the charged surface, the relative permittivity decreases due to depletion of water molecules (volume-excluded effect) and orientational ordering of water dipoles (saturation effect). At the end, the LPB and LB models are generalised by also taking into account the cavity field.     

Contact pairs of RNA with magnesium ions-electrostatics beyond the Poisson-Boltzmann equation

The electrostatic interaction of RNA with its aqueous environment is most relevant for defining macromolecular structure and biological function. The attractive interaction of phosphate groups in the RNA backbone with ions in the water environment leads to the accumulation of positively charged ions in the first few hydration layers around RNA. Electrostatics of this ion atmosphere and the resulting ion concentration profiles have been described by solutions of the nonlinear Poisson-Boltzmann equation and atomistic molecular dynamics (MD) simulations. Much less is known on contact pairs of RNA phosphate groups with ions at the RNA surface, regarding their abundance, molecular geometry, and role in defining RNA structure. Here, we present a combined theoretical and experimental study of interactions of a short RNA duplex with magnesium (Mg²⁺) ions. MD simulations covering a microsecond time range give detailed hydration geometries as well as electrostatics and spatial arrangements of phosphate-Mg²⁺ pairs, including both pairs in direct contact and separated by a single water layer. The theoretical predictions are benchmarked by linear infrared absorption and nonlinear two-dimensional infrared spectra of the asymmetric phosphate stretch vibration which probes both local interaction geometries and electric fields. Contact pairs of phosphate groups and Mg²⁺ ions are identified via their impact on the vibrational frequency position and line shape. A quantitative analysis of infrared spectra for a range of Mg²⁺-excess concentrations and comparison with fluorescence titration measurements shows that on average 20–30% of the Mg²⁺ ions interacting with the RNA duplex form contact pairs. The experimental and MD results are in good agreement. In contrast, calculations based on the nonlinear Poisson-Boltzmann equation fail in describing the ion arrangement, molecular electrostatic potential, and local electric field strengths correctly. Our results underline the importance of local electric field mapping and molecular-level simulations to correctly account for the electrostatics at the RNA-water interface.     

Chemically induced lipid phase separation in model membranes containing charged lipids: A spin label study

The lipid distribution in binary mixed membranes containing charged and uncharged lipids and the effect of Ca²⁺ and polylysine on the lipid organization was studied by the spin label technique. Dipalmitoyl phosphatidic acid was the charged, and spin labelled dipalmitoyl lecithin was the uncharged (zwitterionic) component. The ESR spectra were analyzed in terms of the spin exchange frequency, W_ex. By measuring W_ex as a function of the molar percentage of labelled lecithin a distinction between a random and a heterogeneous lipid distribution could be made. It is established that mixed lecithinphosphatidic acid membranes exhibit lipid segregation (or a miscibility gap) in the fluid state. Comparative experiments with bilayer and monolayer membranes strongly suggest a lateral lipid segregation. At low lecithin concentration, aggregates containing between 25% and 40% lecithin are formed in the fluid phosphatidic acid membrane. This phase separation in membranes containing charged lipids is understandable on the basis of the Gouy-Chapman theory of electric double layers.In dipalmitoyl lecithin and in dimyristoyl phosphatidylethanolamine membranes the labelled lecithin is randomly distributed above the phase transition and has a coefficient of lateral diffusion of D = 2.8·10^?8 cm²/s at 59°C.Addition of Ca²⁺ dramatically increases the extent of phase separation in lecithin-phosphatidic acid membranes. This chemically (and isothermally) induced phase separation is caused by the formation of crystalline patches of the Ca²⁺-bound phosphatidic acid. Lecithin is squeezed out from these patches of rigid lipid. The observed dependence of W_ex on the Ca²⁺ concentration could be interpreted quantitatively on the basis of a two-cluster model. At low lecithin and Ca²⁺ concentration clusters containing about 30 mol% lecithin are formed. At high lecithin or Ca²⁺ concentrations a second type of precipitation containing 100% lecithin starts to form in addition. A one-to-one binding of divalent ions and phosphatidic acid at pH 9 was assumed. Such a one-to-one binding at pH 9 was established for the case of Mn²⁺ using ESR spectroscopy.Polylysine leads to the same strong increase in the lecithin segregation as Ca²⁺. The transition of the phosphatidic acid bound by the polypeptide is shifted from T_t = 47.5° to T_t = 62°C. This finding suggests the possibility of cooperative conformational changes in the lipid matrix and in the surface proteins in biological membranes.     

Molecular dynamics simulation of unsaturated lipid bilayers at low hydration: parameterization and comparison with diffraction studies.

A potential energy function for unsaturated hydrocarbons is proposed and is shown to agree well with experiment, using molecular dynamics simulations of a water/octene interface and a dioleoyl phosphatidylcholine (DOPC) bilayer. The simulation results verify most of the assumptions used in interpreting the DOPC experiments, but suggest a few that should be reconsidered. Comparisons with recent results of a simulation of a dipalmitoyl phosphatidylcholine (DPPC) lipid bilayer show that disorder is comparable, even though the temperature, hydration level, and surface area/lipid for DOPC are lower. These observations highlight the dramatic effects of unsaturation on bilayer structure.     

Insights into the molecular basis of action of the AT1 antagonist losartan using a combined NMR spectroscopy and computational approach

The drug:membrane interactions for the antihypertensive AT1 antagonist losartan, the prototype of the sartans class, are studied herein using an integrated approach. The pharmacophore arrangement of the drug was revealed by rotating frame nuclear Overhauser effect spectroscopy (2D ROESY) NMR spectroscopy in three different environments, namely water, dimethyl sulfoxide (DMSO), and sodium dodecyl sulfate (SDS) micellar solutions mimicking conditions of biological transport fluids and membrane lipid bilayers. Drug association with micelles was monitored by diffusion ordered spectroscopy (2D DOSY) and drug:micelle intermolecular interactions were characterized by ROESY spectroscopy. The localisation of the drug in the micellar environment was investigated by introducing 5-doxyl and 16-doxyl stearic acids. The use of spin labels confirmed that losartan resides close to the micelle:water interface with the hydroxymethyl group and the tetrazole heterocyclic aromatic ring facing the polar surface with the potential to interact with SDS charged polar head groups in order to increase amphiphilic interactions. The spontaneous insertion, the diffusion pathway and the conformational features of losartan were monitored by Molecular Dynamics (MD) simulations in a modeled SDS micellar aggregate environment and a long exploratory MD run (580 ns) in a phospholipid dipalmitoylphosphatidylcholine (DPPC) bilayer with the AT₁ receptor embedded. MD simulations were in excellent agreement with experimental results and further revealed the molecular basis of losartan:membrane interactions in atomic-level detail. This applied integrated approach aims to explore the role of membranes in losartan's pathway towards the AT₁ receptor.     

Interaction of the cholesterol reducing agent simvastatin with zwitterionic DPPC and charged DPPG phospholipid membranes

Simvastatin is a lipid-lowering drug in the pharmaceutical group statins. Interaction of a drug with lipids may define its role in the system and be critical for its pharmacological activity. We examined the interactions of simvastatin with zwitterionic dipalmitoyl phosphatidylcholine (DPPC) and anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar vesicles (MLVs) as a function of temperature at different simvastatin concentrations using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The FTIR results indicate that the effect of simvastatin on membrane structure and dynamics depends on the type of membrane lipids. In anionic DPPG MLVs, high simvastatin concentrations (12, 18, 24 mol%) change the position of the CH₂ antisymmetric stretching mode to lower wavenumber values, implying an ordering effect. However, in zwitterionic DPPC MLVs, high concentrations of simvastatin disorder systems both in the gel and liquid crystalline phases. Moreover, in DPPG and DPPC MLVs, simvastatin has opposite dual effects on membrane dynamics. The bandwidth of the CH₂ antisymmetric stretching modes increases in DPPG MLVs, implying an increase in the dynamics, whereas it decreases in DPPC MLVs. Simvastatin caused broadening of the phase transition peaks and formation of shoulders on the phase transition peaks in DSC curves, indicating multi-domain formations in the phospholipid membranes. Because physical features of membranes such as lipid order and fluidity may be changed with the bioactivity of drugs, opposing effects of simvastatin on the order and dynamics of neutral and charged phospholipids may be critical to deduce the action mechanism of the drug and estimate drug-membrane interactions.     

Chemically induced lipid phase separation in model membranes containing charged lipids: a spin label study.

The lipid distribution in binary mixed membranes containing charged and uncharged lipids and the effect of Ca2+ and polylysine on the lipid organization was studied by the spin label technique. Dipalmitoyl phosphatidic acid was the charged, and spin labelled dipalmitoyl lecithin was the uncharged (zwitterionic) component. The ESR spectra were analyzed in terms of the spin exchange frequency, Wex. By measuring Wex as a function of the molar percentage of labelled lecithin a distinction between a random and a heterogeneous lipid distribution could be made. It is established that mixed lecithin-phosphatidic acid membranes exhibit lipid segregation (or a miscibility gap) in the fluid state. Comparative experiments with bilayer and monolayer membranes strongly suggest a lateral lipid segregation. At low lecithin concentration, aggregates containing between 25% and 40% lecithin are formed in the fluid phosphatidic acid membrane. This phase separation in membranes containing charged lipids is understandable on the basis of the Gouy-Chapman theory of electric double layers. In dipalmitoyl lecithin and in dimyristoyl phosphatidylethanolamine membranes the labelled lecithin is randomly distributed above the phase transition and has a coefficient of lateral diffusion of D = 2.8-10(-8) cm2/s at 59 degrees C. Addition of Ca2+ dramatically increases the extent of phase separation in lecithin-phosphatidic acid membranes. This chemically (and isothermally) induced phase separation is caused by the formation of crystalline patches of the Ca2+-bound phosphatidic acid. Lecithin is squeezed out from these patches of rigid lipid. The observed dependence of Wex on the Ca2+ concentration could be interpreted quantitatively on the basis of a two-cluster model. At low lecithin and Ca2+ concentration clusters containing about 30 mol % lecithin are formed. At high lecithin or Ca2+ concentrations a second type of precipitation containing 100% lecithin starts to form in addition. A one-to-one binding of divalent ions and phosphatidic acid at pH 9 was assumed. Such a one-to-one binding at pH 9 was established for the case of Mn2+ using ESR spectroscopy. Polylysine leads to the same strong increase in the lecithin segregation as Ca2+. The transition of the phosphatidic acid bound by the polypeptide is shifted from Tt = 47.5 degrees to Tt = 62 degrees C. This finding suggests the possibility of cooperative conformational changes in the lipid matrix and in the surface proteins in biological membranes.     

Modification of ion transport in lipid bilayer membranes in the presence of 2,4-dichlorophenoxyacetic acid. II. Suppression of tetraphenylborate conductance and changes of interfacial potentials.

It has been shown that the blocking of negatively charged tetraphenylborate ion transport in phosphatidylcholine (PC)-cholesterol membranes by the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is dominated by suppression of TPhB- diffusion across the membrane interior, rather than by the decrease of adsorption of TPhB- ions at the membrane surface. The blocking effect can be associated with the decrease of electric potential inside the membrane with respect to that of the aqueous medium, this decreases being proportional to the concentration of 2,4-D in the aqueous solution. It has been estimated that 25 - 30% of the total 2,4-D-induced change of the potential difference is between the plane of absorption of TPhB- and the aqueous solution, and the remaining fraction is between the membrane interior and the absorption plane. The results of this study support the dipolar hypothesis of 2,4-D action in lipid membranes. These conclusions are further supported by measurements changes of electric potential difference across air/water and air/lipid monolayer/water interfaces. It has been found that the electric potential of the nonpolar side of the interface decreases in the presence of neutral molecules of 2,4-D and that this effect becomes more prominent in presence of electrolyte. We have confirmed that PC-cholesterol monolayer cannot be considered as a model for half of the bilayer membrane because of the disagreement between the changes of the interfacial potential difference of PC-cholesterol monolayers and those determined from studied of transport of positive and negative ions across bilayer membranes. In contract, we have found close agreement between the 2,4-D-induced changes of electric potential of the lipid hydrocarbon region in glycerolmonooleate (GMO) membranes and GMO monolayers. We suggest that the action of 2,4-D in lipid membranes is not associated with the changes of orientation of dipoles of lipids constituting the membranes, but rather with a layer of 2,4-D molecules absorbed at the nonpolar/polar membrane boundary.     

Membrane dipole potentials, hydration forces, and the ordering of water at membrane surfaces.

We have compared hydration forces, electrical dipole potentials, and structural parameters of dispersions of dipalmitoylphosphatidylcholine (DPPC) and dihexadecylphosphatidylcholine (DHPC) to evaluate the influence of fatty acid carbonyl groups on phospholipid bilayers. NMR and x-ray investigations performed over a wide range of water concentrations in the samples show, that in the liquid crystalline lamellar phase, the presence of carbonyl groups is not essential for lipid structure and hydration. Within experimental error, the two lipids have identical repulsive hydration forces between their bilayers. The higher transport rate of the negatively charged tetraphenylboron over the positively charged tetraphenylarsonium indicates that the dipole potential is positive inside the membranes of both lipids. However, the lack of fatty acid carbonyl groups in the ether lipid DHPC decreased the potential by (118 +/- 15) mV. By considering the sign of the potential and the orientation of carbonyl groups and headgroups, we conclude that the first layer of water molecules at the lipid water interface makes a major contribution to the dipole potential.     

Electrophoresis in protein crystal: nonequilibrium molecular dynamics simulations

Electrophoresis of a mixture of NaCl and CaCl₂ in a lysozyme crystal is investigated using nonequilibrium molecular dynamics (MD) simulations. Upon exposure to an electric field, the stability of lysozyme is found to decrease slightly. This finding is demonstrated by increases in the root mean-square deviations of the heavy atoms of lysozyme, in the solvent-accessible surface area of hydrophobic residues, and in the number of hydrogen bonds between lysozyme and water. The solvent-accessible surface area of hydrophilic residues changes marginally, and the number of hydrogen bonds between lysozyme molecules decreases. Water molecules tend to align preferentially parallel to the electric field, and the dipole moment along the pore axis increases linearly with increasing field strength. Two pronounced layered structures are observed for Na⁺ and Ca²⁺ in the vicinity of protein surface, but only one enriched layer is observed for Cl⁻. The number distributions of all ions are nearly independent of the electric field. The water coordination numbers of all ions are smaller in the crystal than in aqueous bulk solution; however, the reverse is found for the Cl⁻ coordination numbers of cations. Both the water and the Cl⁻ coordination numbers are insensitive to the electric field. Ion diffusivities in the crystal are ∼2 orders of magnitude smaller than those in aqueous bulk solution. The drift velocities of ions increase proportionally to the electric field, particularly at high strengths, and depend on ionic charge and coordination with oppositely charged ions. Electrical current exhibits a linear relationship with the field strength. The zero-field electrical conductivity is estimated to be 0.56 S/m, which is very close to 0.61 S/m as predicted by the Nernst-Einstein equation.     

Surface Charges of the Membrane Crucially Affect Regulation of Na,K-ATPase by Phospholemman (FXYD1)

The human α₁/His₁₀-β₁ isoform of Na,K-ATPase has been reconstituted as a complex with and without FXYD1 into proteoliposomes of various lipid compositions in order to study the effect of the regulatory subunit on the half-saturating Na⁺ concentration (K _1/2) of Na⁺ ions for activation of the ion pump. It has been shown that the fraction of negatively charged lipid in the bilayer crucially affects the regulatory properties. At low concentrations of the negatively charged lipid DOPS (<10 %), FXYD1 increases K _1/2 of Na⁺ ions for activation of the ion pump. Phosphorylation of FXYD1 by protein kinase A at Ser68 abrogates this effect. Conversely, for proteoliposomes made with high concentrations of DOPS (>10 %), little or no effect of FXYD1 on the K _1/2 of Na⁺ ions is observed. Depending on ionic strength and lipid composition of the proteoliposomes, FXYD1 can alter the K _1/2 of Na⁺ ions by up to twofold. We propose possible molecular mechanisms to explain the regulatory effects of FXYD1 and the influence of charged lipid and protein phosphorylation. In particular, the positively charged C-terminal helix of FXYD1 appears to be highly mobile and may interact with the cytoplasmic N domain of the α-subunit, the interaction being strongly affected by phosphorylation at Ser68 and the surface charge of the membrane.     

The modulation of ion channels by the inhalation general anaesthetics. A1H-NMR investigation using unilamellar phospholipid membranes

The modulation of a variety of mechanisms of channel-mediated transport across unilamellar phospholipid membranes by a range of halogenated inhalation general anaesthetics (chloroform, enflurane, halothane and methoxyflurane) was investigated using 1H-NMR spectroscopy. Transport of the probe ion Pr3+ across egg yolk phosphatidylcholine (PC) and dipalmitoyl phosphatidylcholine (DPPC) vesicular membranes in the presence of the channel forming polypeptides alamethicin 30 and melittin, and the polyene antibiotic nystatin, as well as the degree of vesicular lysis at the gel to liquid-crystal phase transition of DPPC vesicles was monitored. The observation that the inhalation general anaesthetics inhibit such membrane permeability independently of the channel system or type of lipid used, suggests that hydrogen-bonded water structure and/or hydrogen-bonding centres at dipolar lipid-polypeptide interfaces, can be likely sites of action of the general anaesthetics.     

Effect of membrane tension on the electric field and dipole potential of lipid bilayer membrane

The dipole potential of lipid bilayer membrane controls the difference in permeability of the membrane to oppositely charged ions. We have combined molecular dynamics (MD) simulations and experimental studies to determine changes in electric field and electrostatic potential of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid bilayer in response to applied membrane tension. MD simulations based on CHARMM36 force field showed that electrostatic potential of DOPC bilayer decreases by ~45mV in the physiologically relevant range of membrane tension values (0 to 15dyn/cm). The electrostatic field exhibits a peak (~0.8×10(9)V/m) near the water/lipid interface which shifts by 0.9? towards the bilayer center at 15dyn/cm. Maximum membrane tension of 15dyn/cm caused 6.4% increase in area per lipid, 4.7% decrease in bilayer thickness and 1.4% increase in the volume of the bilayer. Dipole-potential sensitive fluorescent probes were used to detect membrane tension induced changes in DOPC vesicles exposed to osmotic stress. Experiments confirmed that dipole potential of DOPC bilayer decreases at higher membrane tensions. These results are suggestive of a potentially new mechanosensing mechanism by which mechanically induced structural changes in the lipid bilayer membrane could modulate the function of membrane proteins by altering electrostatic interactions and energetics of protein conformational states.