Implicit-solvent mesoscale model based on soft-core potentials for self-assembled lipid membranes

An efficient implicit-solvent model for self-assembled lipid bilayers is presented and analyzed using Langevin molecular dynamics simulations. The model is based on soft interactions between particles and short-range attractive interaction between lipid tails, leading for the self-assembly of a lipid bilayer without an explicit solvent. This allows for efficient simulations of large membranes over long times. The model exhibits a fluid phase at high temperatures and a gel phase at low temperatures, identified with the Lbeta-phase. The melting transition is investigated via analysis of the diffusivity of the lipid molecules, the chain-orientational order parameter, the sixfold bond-orientational order parameter, and the positional and bond-orientational correlation functions. The analysis suggests the existence of a hexatic phase over a narrow range of temperatures around the melting transition. The elastic properties of the membrane in the fluid phase are also investigated.     

Thin-thick surface phase coexistence and boundary tension of the square-well fluid on a weak attractive surface

Prewetting transition is studied for the square-well fluid of attractive-well diameter lambda(ff)sigma(ff)=1.5 in the presence of a homogeneous surface modeled by the square-well potential of attractive well from 0.8sigma(ff) to 1.8sigma(ff). We investigate surface phase coexistence of thin-thick film transition using grand-canonical transition matrix Monte Carlo (GC-TMMC) and histogram reweighting techniques. Molecular dynamics (MD) and GC-TMMC are utilized to predict the properties of the fluid for various surface fluid affinities. Occurrences of prewetting transition with the variation of surface affinity are observed for a domain of reduced temperature from T(*)=0.62 to 0.75. We have used MD and GC-TMMC+finite size scaling (FSS) simulations to calculate the boundary tension as a function of temperature as well as surface affinity. Boundary tensions via MD and GC-TMMC+FSS methods are in good agreement. The boundary tension increases with the decrease of wall-fluid affinity. Prewetting critical properties are calculated using rectilinear diameter approach and scaling analysis. We found that critical temperature and density increase with the decrease of wall-fluid affinity.     

Study of the stabilization energies of halide-water clusters: an application of first-principles interaction potentials based on a polarizable and flexible model

The aim of this work is to compute the stabilization energy E(stab)(n) of [X(H(2)O)(n)](-) (X identical with F, Br, and I for n=1-60) clusters from Monte Carlo simulations using first-principles ab initio potentials. Stabilization energy of [X(H(2)O)(n)](-) clusters is defined as the difference between the vertical photodeachment energy of the cluster and the electron affinity of the isolated halide. On one hand, a study about the relation between cluster structure and the E(stab)(n) value, as well as the dependence of the latter with temperature is performed, on the other hand, a test on the reliability of our recently developed first-principles halide ion-water interaction potentials is carried out. Two different approximations were applied: (1) the Koopmans' theorem and (2) calculation of the difference between the interaction energy of [X(H(2)O)(n)](-) and [X(H(2)O)(n)] clusters using the same ab initio interaction potentials. The developed methodology allows for using the same interaction potentials in the case of the ionic and neutral clusters with the proviso that the charge of the halide anion was switched off in the latter. That is, no specific parametrization of the interaction potentials to fit the magnitude under study was done. The good agreement between our predicted E(stab)(n) and experimental data allows us to validate the first-principles interaction potentials developed elsewhere and used in this study, and supports the fact that this magnitude is mainly determined by electrostatic factors, which can be described by our interaction potentials. No relation between the value of E(stab)(n) and the structure of clusters has been found. The diversity of E(stab)(n) values found for different clusters with similar interaction energy indicates the need for statistical information to properly estimate the stabilization energy of the halide anions. The effect of temperature in the prediction of the E(stab)(n) is not significant as long as it was high enough to avoid cluster trapping into local equilibrium configurations which guarantees an appropriate sampling of the configurational space. Parallel tempering method was applied in particular cases to guarantee satisfactory sampling of clusters at low temperature.     

Thermotropic and barotropic phase transitions of dialkyldimethylammonium bromide bilayer membranes: effect of chain length

The bilayer phase transitions of dialkyldimethylammonium bromides (2C(n)Br; n = 12, 14, 16) were observed by differential scanning calorimetry and high-pressure light-transmittance measurements. Under atmospheric pressure, the 2C(12)Br bilayer membrane underwent the stable transition from the lamellar crystal (L(c)) phase to the liquid crystalline (L(α)) phase. The 2C(14)Br bilayer underwent the main transition from the metastable lamellar gel (L(β)) phase to the metastable L(α) phase in addition to the stable L(c)/L(α) transition. For the 2C(16)Br bilayer, moreover, three kinds of phase transitions were observed: the metastable main transition, the metastable transition from the metastable lamellar crystal (L(c(2))) phase to the metastable L(α) phase, and the stable lamellar crystal (L(c(1)))/L(α) transition. The temperatures of all the phase transitions elevated almost linearly with increasing pressure. The temperature (T)-pressure (p) phase diagrams of the 2C(12)Br and 2C(14)Br bilayers were simple, but that of the 2C(16)Br bilayer was complex; that is, the T-p curves for the metastable main transition and the L(c(2))/L(α) transition intersect at ca. 25 MPa, which means the inversion of the relative phase stability between the metastable phases of L(β) and L(c(2)) above and below the pressure. Moreover, the T-p curve of the L(c(2))/L(α) transition was separated into two curves under high pressure, and as a result, the pressure-induced L(c(2P)) phase appeared in between. Thermodynamic quantities for phase transitions of the 2C(n)Br bilayers increased with an increase in alkyl-chain length. The chain-length dependence of the phase-transition temperature for all kinds of transitions observed suggests that the stable L(c(1))/L(α) transition incorporates the metastable L(c(2))/L(α) transition in the bilayers of 2C(n)Br with shorter alkyl chains, and the main-transition of the 2C(12)Br bilayer would occur at a temperature below 0 °C.     

On the fluid phase behaviour of fluid binary mixtures using the Yukawa fluid molecular model

By expanding Ginoza’s mean spherical approximation (MSA) results in an inverse-temperature expansion, Henderson et al. obtained explicit results for the thermodynamic functions of a pure Yukawa fluid. We have recently published explicit results for the coefficients in an inverse-temperature expansion of the thermodynamic functions for the MSA for mixtures of Yukawa fluids. Attention is drawn to the fact that the MSA in the Ginoza formulation, does not always yield a convergent solution. The expansion used in this paper will always yield a result. In this work we present our investigations of the fluid phase diagram of Yukawa binary mixtures by considering an expansion of the MSA Helmholtz free energy up to the fifth order of the inverse-temperature expansion. The calculated fluid phase diagrams for Yukawa binary mixtures are similar to those of real mixtures.     

Biomimetic particles: optimization of phospholipid bilayer coverage on silica and colloid stabilization

The effect of ionic strength and pH on phosphatidylcholine (PC) adsorption from vesicles on silica nanoparticles was investigated over a range of NaCl concentrations (0.1-150 mM) at pH 6.3 and 7.4 from determination of adsorption isotherms, colloid stability, particle sizing, and zeta-potentials. At and above 10 mM ionic strength, pH 6.3, high-affinity adsorption isotherms with limiting adsorption indicative of one-bilayer deposition on each silica particle were obtained. At 10 mM ionic strength, adsorption isotherms indicated lower affinity between PC and silica at pH 7.4 than at pH 6.3, suggesting a role of hydrogen bonding between silanol on silica and phosphate on PC in promoting bilayer deposition at low pH. Under conditions where high affinity and bilayer deposition were achieved, silica sedimentation documented from photographs was absent, suggesting particle stabilization induced by bilayer coverage. However, at physiological (150 mM NaCl) or close to physiological ionic strength (140 mM NaCl), the large colloid stability similarly achieved at pH 6.3 or 7.4 suggested the major role of van der Waals attraction between the PC bilayer vesicle and silica particle in determining bilayer deposition. The effect of increasing ionic strength was increasing van der Waals attraction, which caused PC vesicle disruption with bilayer deposition and bilayer-induced silica stabilization.     

Ion permeability through bilayer lipid membranes for biosensor development: control by chemical modification of interfacial regions between phase domains.

Based on the results of studies on cystic fibrosis, which implicated hydroxystearic acid (HSA) as a contributing factor in altered biomembrane function, solvent-free bilayer lipid membranes (BLMs) and monolayer films were prepared from a lipid mixture containing (by mass) 34% phosphatidylcholine, 19% dipalmitoylphosphatidyl serine, 47% cholesterol and variable amounts of 10- and 12-HSA (0-50%). Ion currents, resulting from K+ permeation through BLMs that were supported in 0.1 mol dm-3 KCl solutions buffered to pH 7.4, were monitored with use of a d.c. circuit. The structures of monolayer films at the air-water interface of a Langmuir-Blodgett trough were studied by pressure-area correlations and by further correlation with microscopic phase separation as revealed by fluorescence microscopy. In order to elucidate the role of the hydroxyl moieties in ion permeability, the transmembrane ion current was corrected for the effect of the negative surface charge of the carboxylic acid by replacement of the HSA component with stearic acid. The ion current was found to increase with the molar proportion of the HSAs. Two models for ion conduction through BLMs were considered: 'hopping' via hydrophilic sites within the hydrophobic zone of the BLMs, introduced by the hydroxyl moiety of 10- or 12-HSA; and transport through interfacial regions between phase domains that represent areas of low steric density and low structural order within monolayers. Although the two mechanisms are not distinct, the ion permeability results indicate a change in the response of ion current to HSA concentration at 35 mol-%, suggesting a change in the relative proportion of the mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)     

A minisensor for the rapid screening of atenolol in pharmaceutical preparations based on surface-stabilized bilayer lipid membranes with incorporated DNA

This work describes an electrochemical technique that is suitable for the rapid and sensitive screening of atenolol based on surface-stabilized bilayer lipid membranes (s-BLMs) composed from egg phosphatidylcholine (PC). The interactions of atenolol with s-BLMs produced electrochemical ion current increases that reproducible appeared within a few seconds after the exposure of the membranes to the drug. The current signal increase was related to the concentration of atenolol in bulk solution in the micromolar range. The present lipid film-based sensor provided fast response (i.e. on the order of a few seconds) to alterations of atenolol concentration (20 to 200 micro M) in electrolyte solution. ssDNA incorporated into s-BLMs can interact with atenolol, and decreased the detection limit of this drug by one order of magnitude. The oligomers used were single stranded deoxyribonucleic acids: thymidylic acid icosanucleotide terminated with a C-16 alkyl chain to assist incorporation into s-BLMs (5'-hexadecyl-deoxythymidylic acid icosanucleotide, dT(20)-C(16)). The electrochemical transduction of the interactions of atenolol with s-BLMs was applied in the determination of these compounds in pharmaceutical preparations by using the present minisensor.     

Peculiarities of the DNA hybridization on the surface of bilayer lipid membranes

The method of electrostriction was applied to study the peculiarities of interaction of short oligonucleotides with free standing (BLM) and supported lipid membranes (sBLM) and of the duplex formation between complementary oligonucleotides on a membrane surface. The 15-mer single stranded DNA (pentadecathymidylate-(dT)(15)) was modified either with cholesterol (CH(dT)(15)) or by palmitoyl chain (C16(dT)(15)). The interaction of CH(dT)(15) with free standing BLM or with BLM formed on an agar or gold support was accompanied by sharp increase of elasticity modulus in direction perpendicular to the membrane plane ,E( perpendicular), and by increase of surface potential. In contrast, C16(dT)(15) did not induce substantial changes of elasticity modulus, however, the surface potential was changed in a similar manner as for CH(dT)(15). Hybridization of DNA following addition of complementary chain (dA)(15) has been accompanied by a small decrease of elasticity modulus and by a slight increase of surface potential. Both the incorporation of chemically modified oligonucleotides into the lipid bilayer as well as hybridization of DNA are not cooperative processes as has been demonstrated by analysis using Scatchard plot of corresponding values.     

Tethered bilayer lipid membranes on mixed self-assembled monolayers of a novel anchoring thiol: impact of the anchoring thiol density on bilayer formation

Tethered bilayer lipid membranes (tBLMs) are designed on mixed self-assembled monolayers (SAMs) of a novel synthetic anchoring thiol, 2,3-di-o-palmitoylglycerol-1-tetraethylene glycol mercaptopropanoic acid ester (TEG-DP), and a new short dilution thiol molecule, tetraethylene glycol mercaptopropanoic acid ester (TEG). tBLM formation was accomplished by self-directed fusion of small unilamellar vesicles of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine. The influence of the dilution of the anchoring thiol molecule in the SAM on the vesicle fusion process and on the properties of the resulting tBLMs is studied. It is observed by quartz crystal microbalance that vesicle fusion is a one-step process for a pure TEG-DP SAM as well as for mixed SAMs containing a high concentration of the anchoring thiol. However, upon dilution of the anchoring thiol to moderate concentrations, this process is decelerated and possibly follows a pathway different from that observed on a pure TEG-DP SAM. Electrochemical impedance spectroscopy is used to qualitatively correlate the composition of the SAM to the electrical properties of the tBLM. In this paper we also delineate the necessity of a critical concentration of this anchoring TEG-DP thiol as a requisite for inducing the fusion of vesicles to form a tBLM.     

A second generation mesoscopic lipid bilayer model: connections to field-theory descriptions of membranes and nonlocal hydrodynamics

A new mesoscopic membrane model is developed in order to examine long-wavelength structural and dynamical membrane phenomena. Two different explicit mesoscopic solvent models are employed. The first mesoscopic solvent is denoted the big liquid oscillating blob system, which is parametrized to model water at a coarse-grained level and is motivated by a Langevin-like approach; the resulting membrane dynamics predict a solvent viscosity dependence consistent with the known viscosity of water. The second mesoscopic solvent is a Weeks-Chandler-Anderson model. Here, it is found that the correct mesoscopic hydrodynamic scaling of the membrane undulation dynamics is still preserved, although accelerated. When the behavior of the two membranes in close proximity to one another is examined, very little correlated motion is observed. However, the theoretically predicted scaling of the entropic undulation energy is confirmed, demonstrating that the entropic interaction between two membranes becomes increasingly repulsive with decreasing separation.     

Biophysical aspects of agar-gel supported bilayer lipid nembranes: a new method for forming and studying planar bilayer lipid membranes

Conventional bilayer lipid membranes (BLMs), formed by either the painting method or the Langmuir-Blodgett technique, lack the desired stability. This paper presents a simple method for forming long-lived BLMs on agar-gel supports. The supported BLM reported has a greatly improved mechanical stability and also has desirable dynamic properties. These self-assembled BLMs are of significant interest, in view of their similarity of biological membranes, their molecular dimension and their spontaneous formation.     

A prototype for the chemosensing of Ba2+ based on self-assembling fluorescence enhancement

[STRUCTURE: SEE TEXT] Barium ion can be revealed at the micromolar concentration level by the blue-green fluorescence which arises upon the self-assembling process involving the metal ion and a novel bis-15-crown-5-naphthalenediimide derivative.     

Phasepy: A Python based framework for fluid phase equilibria and interfacial properties computation

Phasepy is a Python based package for fluid phase equilibria and interfacial properties calculation from equation of state (EoS). Phasepy uses several tools (i.e., NumPy, SciPy, Pandas, Matplotlib) allowing use Phasepy under Jupyter Notebooks. Phasepy models phase equilibria with the traditional ϕ –γ and ϕ –ϕ approaches, where ϕ (fugacity coefficient) can be modeled as a perfect gas, virial gas or EoS fluid, whereas γ (activity coefficient) can be described by conventional models (NRTL, Wilson, Redlich-Kister expansion, and the group contribution modified-UNIFAC). Interfacial properties are based on the square gradient theory couple to ϕ –ϕ approach. The available EoSs are the cubic EoS family extended to mixtures through the quadratic, modified-Huron-Vidal, and Wong-Sandler mixing rules. Phasepy allows to analyze phase stability, compute phase equilibria, interfacial properties, and optimize their parameters for vapor–liquid, liquid–liquid, and vapor–liquid–liquid equilibria for multicomponent mixtures. Phasepy implementation, and robustness are illustrated for binary and ternary mixtures.     

A vibrational Hamiltonian model for triatomic molecules based on the Kratzer and Poschl Teller potentials

A Hamiltonian model to describe molecular vibrations of triatomic molecules is proposed. The Hamiltonian is based on the use of the Kratzer potential variable for the stretching motions and a perturbed Poschl Teller potential for the bending one. The perturbation and variational treatments to compute the vibrational energies of this Hamiltonian can be developed using a zero-order system that includes part of the couplings between the stretching and bending motions. All the matrix elements involved in these calclations can be then evaluated in closed form. A numerical application to the HCN molecule is made. © 1994 John Wiley & Sons, Inc.     

Biomimetic sensing based on chemically induced assembly of a signaling DNA aptamer on a fluid bilayer membrane

The adenosine aptamer was split into two halves and linked to a fluid liposome surface; addition of adenosine resulted in aptamer assembly, which did not occur if the split aptamer was attached to silica nanoparticles, demonstrating the feasibility of using aptamer probes to study diffusion within lipid membranes.     

Gauging the effect of impurities on lipid bilayer phase transition temperature

We report on the gel-to-fluid phase transition behavior of unilamellar vesicles formed with 1,2-dimyristoyl-sn-phosphatidylcholine (14:0 DMPC). We have interrogated the gel-to-fluid transition temperature of these bilayer structures using the chromophore perylene incorporated in their nonpolar region. We observe a discontinuous change in the reorientation time of perylene sequestered within the bilayer at the known melting transition temperature of 14:0 DMPC, 24 degrees C. The perylene reorientation data reveal a local viscosity of 14.5 +/- 2.5 cP in the gel phase, and 8.5 +/- 1.5 cP in the fluid phase. We have also incorporated small amounts of 1,2-dimyristoleoyl-sn-glycero-3-phosphocholine (14:1 DMPC) into these unilamellar vesicles and find that the melting transition temperature for these bilayers varies in a regular manner with the amount of 14:1 DMPC present. These data demonstrate that very little "contaminant" is required to cause a substantial change in the gel-to-fluid transition temperature, even though these contaminants do not alter the viscosity of the bilayer sensed by perylene, either above or below the melting transition.     

Impedance measurements of self-assembled lipid bilayer membranes on the tip of an electrode

Supported lipid membranes were self-assembled on the tip of a freshly cleaved silver wire, in the presence of an appropriate polarization voltage, to facilitate, during the membrane formation, the organization of the lipids into an ordered structure. Radiowave impedance spectroscopy measurements have been carried out to provide information on the relaxation properties of the system. We have measured the conductometric and dielectric properties of bilayers built up of different lipids [dipalmitoylphosphatidic acid (DPPA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), linoleic acid (LIN)] in a wide frequency range (from 10(3) to 10(6) Hz) and in electrolyte solutions of different ionic strengths, in the presence of uni-univalent (KCl) and di-univalent (CaCl(2), MgCl(2), ZnCl(2)) electrolytes. This made it possible to measure the influence of different cations and different lipid compositions on the membrane properties. In particular, we have found a different capacitive behaviour of the supported lipid bilayer membrane (s-BLM) structure in the presence of different counterions in the electrolyte solution. This peculiarity offers the opportunity for the preparation of a variety of biosensors with diverse applications in membrane biophysics, biochemistry and biotechnology.