Difference in surface activities between uncharged and charged local anesthetics: correlation with their anesthetic potencies

The surface activities of six uncharged local anesthetics, dibucaine (DC), bupivacaine (BC), lidocaine (LC), mepivacaine (MC), benzocaine (BzC), and benzyl alcohol (BzOH) were investigated by taking surface tension measurements of their aqueous solutions. The surface densities of the uncharged anesthetics were calculated from the application of thermodynamic equations to the surface tension data. The surface activities for uncharged anesthetics became higher in the order of their hydrophobicities, BzOH相似文献   

Distribution of local anesthetics in lipid membranes

Absorption of local anesthetics into lipid membranes and adsorption onto their surfaces were studied as a function of the pH of aqueous bulk solutions by measuring lipid vesicle electrophoretic mobility, the partition of the anesthetics between the aqueous and membrane phases by the use of fluorescence and radioactive tracer methods, and the effect of the anesthetics on interfacial tension of lipid monolayers formed at the oil/aqueous interface.

At a pH much lower than the pK_a value of the local anesthetic, the charged form of the local anesthetic was only adsorbed onto the membrane surface, as determined from vesicle electrophoretic mobility, radioisotope tracer and the monolayer surface tension studies. Surface partition coefficients of the charged form of the local anesthetics on phosphatidylcholine and phosphatidylserine membranes were obtained from the data of electrophoretic mobilities for lipid vesicles. The surface partition coefficients of various local anesthetics paralleled those of the bulk partition coefficients.

As the pH of the solutions increased, the adsorbed amount of the charged form of the anesthetic at the membrane interface decreased, while the absorption of the uncharged form of the local anesthetic into the membrane increased. The total amount of local anesthetic adsorbed per unit area of the membrane generally increased as the pH of the solution increased. This was also observed from the measurements of the fluorescence of local anesthetics adsorbed into the membranes. At lower pH than that corresponding to the pK_a value of the local anesthetic, the amount of anesthetic adsorbed depended greatly upon the membrane surface charge. At a higher pH than its pK_a, it did not depend appreciably on the surface charge density of the membrane but did depend on the bulk partition coefficients between the aqueous and oil phases.     

Preferential partitioning of uncharged local anesthetics into the surface-adsorbed film

The surface tension and pH of aqueous solutions of three hydrochloric acid (HCl) - uncharged anesthetic (mepivacaine (MC), bupibacaine (BC) and dibucaine (DC)) mixtures were measured as a function of total molality and composition of local anesthetic in order to investigate the competitive surface-adsorption of uncharged and charged local anesthetics. The behavior of the surface tension versus total molality and pH versus total molality curves remarkably changed at the composition corresponding to an equimolar mixture. The pH measurements showed that uncharged and charged forms coexisted only at compositions more than the equimolar mixture. The partitioning quantities of respective uncharged and charged anesthetics into the surface-adsorbed film were estimated from their surface densities calculated thermodynamically. The greater quantity of uncharged anesthetics existed in the adsorbed film at the coexisting composition, that is, the uncharged anesthetics adsorbed more preferentially than charged ones. The relative ease with which uncharged anesthetics transferred into the surface-adsorbed film was proportional to the hydrophobicities and well correlated the anesthetic potencies. At compositions in the vicinity of physiological pH (ca. 7.4), the bulk solution is more abundant in charged anesthetics than uncharged ones, whereas the uncharged molecules is conversely more abundant in the surface region. The present results clearly imply that the surface-active molecule of local anesthetic in the physiological pH is the uncharged form and the partitioning is greatly dependent on the hydrophobicity among the anesthetics.     

Photocurrent of purple membrane adsorbed onto a thin polymer film: action characteristics of the local anesthetics

The proton pumping activity of bacteriorhodopsin (bR) in the purple membrane adsorbed onto a thin polymer film as a solid support for electrical measurements has been examined in the presence of local anesthetics and 1-alcohols as an anesthetic model. This membrane adsorbed system provided high reproducibility of the photocurrents in bR due to the mechanical and the chemical stability and the electric properties of the thin polymer film. As the concentrations of the local anesthetics increased, the photocurrents generated by the proton pump of bR were cooperatively suppressed and the changes in the photocurrents were reversible. From the dose–response curves for the anesthetics, the concentration (EC₅₀) required for a 50% suppression showed a marked specificity in the order of lidocaine>bupivacaine>tetracaine>dibucaine. The suppression of the photocurrent in bR was more effective for the uncharged form of the local anesthetics than for the charged one. The absorption and fluorescence spectra suggested that the charged form of the anesthetics was bound to the purple membrane surface, while their uncharged form interacted with the hydrophobic portions of the purple membrane interior rather than with the membrane surface. From the dose–response curves for the 1-alcohols, an increase in hydrophobicity in their molecules effectively suppressed the photocurrent of bR. We found that the binding of hydrophobic organic cations such as tetracaine hydrochloride and bupivacaine hydrochloride to the blue membrane with loss of the proton pump, which was prepared by removal of the cations from the purple membrane, could regenerate the proton pumping activity. The photocurrent in bR in the purple membrane adsorbed onto a thin solid film sensitively responded to different local anesthetics.     

Thermodynamic study of benzocaine insertion into different lipid bilayers

Despite the general consensus concerning the role played by sodium channels in the molecular mechanism of local anesthetics, the potency of anaesthetic drugs also seems to be related with their solubility in lipid bilayers. In this respect, this work represents a thermodynamic study of benzocaine insertion into lipid bilayers of different compositions by means of molecular dynamics simulation. Thus, the free energy profiles associated with benzocaine insertion into symmetric lipid bilayers composed of different proportions of dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine were studied. From the simulation results, a maximum in the free energy (ΔG) profile was measured in the region of the lipid/solution interface. This free energy barrier appears to be very much dependent on the lipid composition of the membrane. On the other hand, the minimum free energy (ΔG) within the bilayer remained almost independent of the lipid composition of the bilayer. By repeating the study at different temperatures, it was seen how the spontaneity of benzocaine insertion into the lipid bilayer is due to an increase in the entropy associated with the process.     

Supported lipid bilayer formation by the giant vesicle fusion induced by vesicle–surface electrostatic attractive interaction

The effect of the electrostatic attractive force between giant unilamellar vesicles (GUVs) and the SiO₂ surface on the formation of a Ca²⁺-free supported lipid bilayer (SLB) was investigated by atomic force microscopy and fluorescence microscopy. When negatively charged GUVs were incubated for 1 h without Ca²⁺, the surface coverage of lipid bilayer was <1% on the SiO₂ surface. In contrast, a high coverage was obtained without addition of Ca²⁺ on the positively charged surface modified by aminopropyldimethylethoxysilane, and the coverage of SLBs decreased with increasing KCl concentrations. The thickness of the water layer under SLB was reduced by modification of APS.     

Determination of the lipid bilayer breakdown voltage by means of linear rising signal

Electroporation is characterized by formation of structural changes within the cell membrane, which are caused by the presence of electrical field. It is believed that "pores" are mostly formed in lipid bilayer structure; if so, planar lipid bilayer represents a suitable model for experimental and theoretical studies of cell membrane electroporation. The breakdown voltage of the lipid bilayer is usually determined by repeatedly applying a rectangular voltage pulse. The amplitude of the voltage pulse is incremented in small steps until the breakdown of the bilayer is obtained. Using such a protocol each bilayer is exposed to a voltage pulse many times and the number of applied voltage pulses is not known in advance. Such a pre-treatment of the lipid bilayer affects its stability and consequently the breakdown voltage of the lipid bilayer. The aim of this study is to examine an alternative approach for determination of the lipid bilayer breakdown voltage by linear rising voltage signal. Different slopes of linear rising signal have been used in our experiments (POPC lipids; folding method for forming in the salt solution of 100 mM KCl). The breakdown voltage depends on the slope of the linear rising signal. Results show that gently sloping voltage signal electroporates the lipid bilayer at a lower voltage then steep voltage signal. Linear rising signal with gentle slope can be considered as having longer pre-treatment of the lipid bilayer; thus, the corresponding breakdown voltage is lower. With decreasing the slope of linear rising signal, minimal breakdown voltage for specific lipid bilayer can be determined. Based on our results, we suggest determination of lipid bilayer breakdown voltage by linear rising signal. Better reproducibility and lower scattering are obtained due to the fact that each bilayer is exposed to electroporation treatment only once. Moreover, minimal breakdown voltage for specific lipid bilayer can be determined.     

Molecular interactions between phospholipids and mangostin in a lipid bilayer

Molecular interactions between phospholipids and mangostin in a lipid bilayer have been investigated in terms of the maximum additive concentration (MAC) of mangostin in liposomes, the surface potential, particle size, microscopic-viscosity and microscopic-polarity of liposomes, and the permeability of glucose. The mangostin used is a natural product extract: 1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9-xanthenenone.

The MAC of mangostin was fairly dependent upon the nature of the liposomes (uncharged, negatively charged or positively charged). Solubilization of mangostin in the liposomal bilayer resulted in both an increase in the negative charge on the liposomal surface, strenghthening the state of the bilayer membrane, and a depression in the release of the glucose involved. Mangostin was found to temporarily stabilize the liposomal bilayer, although the bilayer membrane is still unstable in the long run.     

Effects of lidocaine-HCl salt and benzocaine on the expansion of lipid monolayers employed as bio-mimicking cell membrane

Effects of lidocaine-HCl salt and benzocaine on the expansion of lipid monolayers employed as bio-mimicking cell membrane were investigated using Langmuir-Blodgett film balance to figure out the molecular mechanism for anesthesia by these local anesthetics. Lidocaine-HCl salt in subphase expanded the monolayer of phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE). Benzocaine was not mixed with lipids in the monolayer, but the monolayer of lipids on the surface of water saturated with benzocaine was expanded same as the case of lidocaine-HCl salt. Even though this study can not explain the whole molecular mechanism for anesthesia by lidocaine-HCl salt and benzocaine, it can be asserted from the results of this study that the expansion of cell membrane by lidocaine-HCl salt and benzocaine contribute, at least partially, to the generation of anesthesia.     

Competitive adsorption of Ca and local anesthetics on lipid membrane surfaces

Adsorption fo tertriary amine local anesthetics and Ca²⁺ onto lipid membranes having various negative surface charge densities was studied by measuring lipid vesicle electrophoretic mobility.

As the surface charge density of the membrane was reduced, the adsorption of the local anesthetics dominated that of the divalent cation. For a relatively high negatively charged membrane, the adsorption of both local anesthetic and Ca²⁺ became comparable and competitive.

It is deduced that the major factor for the adsorption of local anesthetic onto lipid membranes is due to simple physical partitioning between aqueous and membrane phases, and not due to ionic type of binding as seen for divalent cations with membranes. However, the adsorption of anesthetics is influenced by the surface potential of membranes which is in turn related to the surface concentration of local anesthetics near the membrane.

The amounts of competitive adsorption of divalent cations and local anesthetics are analyzed with respect to their bulk concentrations and various surface charge densities of the membranes. With the results of the above studies, a possible interpretation for the interaction site as well as the mode of adsorption of local anesthetics onto axon membranes is made in relation to divalent cation concentrations in the bulk phases.     

High open-circuit voltage in UV photovoltaic cell based on polymer/inorganic bilayer structure

Polymer/inorganic hybrid ultra violet (UV) photovoltaic device is fabricated by using poly(N-vinyl-carbazole) (PVK) and zinc sulfide (ZnS). The device shows promising photovoltaic characteristics with a high open-circuit voltage of 1.65 V, and a short-circuit current of 46.8 μA/cm² under the illumination of 340 nm UV light with the intensity of 14 mW/cm². Besides, much correlative photocurrent spectra of the device under forward and reverse applied bias manifest the transport mechanism of charge carriers in PVK/ZnS bilayer systems.     

Amphiphile bilayer films from DPPC: bilayer lipid membranes and Newton black films

Amphiphile bilayer films are obtained from 1,2 dipalmitoyl-glycero-3-phosphocholine (DPPC): bilayer lipid membranes (BLM) and Newton black films (NBF), through thinning of the respective thin liquid films, thus allowing for a very precise determination of the moment of their formation. Stability (or rupture) and formation of BLM and NBF are considered from a unified point of view with the microscopic theory of Kashchiev–Exerowa [J. Colloid Interface Sci., 77 (1980) 501–511], based on the formation of nanoscopic holes in them. BLM and NBF are obtained and studied with the microinterferometric method of Scheludko–Exerowa in its contemporary version. The equivalent thickness of both BLM (in benzene solution between two water phases with 0.1 M NaCl) and NBF in aqueous DPPC solution (in the presence of 0.1 M NaCl) is determined as being h_w = 7.0 nm for BLM and h_w = 7.8 nm for NBF. By means of the dependences: BLM lifetime versus DPPC concentration and probability for BLM formation versus DPPC concentration, it is established that there exist metastable BLM and stable NBF. The good fit between the experimental results of τ(C) dependence and theory in the case of BLM allow to determine the three constants: pre-exponential factor A = 1.5 × 10⁻³ s, related to the process kinetics; constant B = 20.2 ± 0.2, related to the specific hole energy γ = 1.7 × 10⁻¹¹ J/m and the equilibrium concentration C_e = 6 × 10⁻⁴ ± 7.2 × 10⁻⁶ m/l. The specific hole linear energy γ = 1.7 × 10⁻¹¹ J/m determined as well as the binding energy Q between first neighbor molecules in the bilayers Q = 1.48 × 10⁻¹⁹ J (36 kT) are lower than the ones determined for DPPC foam bilayer in gel state γ = 9.1 × 10⁻¹¹ J/m and Q = 55 kT. This means that interaction is weaker in the case of BLM. The critical concentration C_c at which bilayer formation starts is: for BLM C_c = 30 μg/ml and for NBF C_c = 70 μg/ml. This concentration characterizes quantitatively the formation of the amphiphile bilayer and is a very useful parameter that can be used for various purposes.     

Homogeneity, electrical resistivity and lateral diffusion of lipid bilayers coupled to polyelectrolyte multilayers

The electrostatic coupling of charged phospholipid bilayers with polyelectrolyte multilayers is studied varying the lipid charge density, multilayer composition and preparation conditions. It is shown that in all cases the bilayer is insufficiently insulating for meaningful electrochemical studies. Homogeneity on a light microscopical length scale was obtained by two methods: vesicle fusion into bilayers and deposition from monolayers by the Langmuir–Schäfer (LB/LS) technique. Largest progress was achieved aiming for lateral diffusion comparable to an uncoupled bilayer. For this mixtures with 10% charged (DOPA) and 90% uncharged (DMPC) lipid were prepared that exhibited sufficient anchoring density and at the same time a fluid DMPC phase on going above the main phase transition at 24°C. This yielded diffusion coefficients in aqueous environment above 1 μm² s⁻¹ with almost no immobile fractions.     

Estimates of the intramembrane field through the harmonics of capacitive current in inhomogeneous bilayer lipid membranes

Intramembrane field gives information about localisation of fixed charges or dipoles inside the lipid bilayer. There is systematic discrepancy between field estimates made by various methods. The possible reason of this discrepancy can be attributed to the misinterpretation of the data in the frames of the methods used. It stands for the method that is based on the compensation of the 2nd harmonic of capacitive current generated due to electrostriction phenomenon if sine voltage is applied to the bilayer. The theoretical grounds of the method mentioned are oversimplified because membrane heterogeneity has not been taken into consideration. The purpose of the work is the analysis of the generation of harmonics of capacitive current in inhomogeneous bilayer if intramembrane charges are located at different depth. The results of the study enable one to determine the position of intramembrane charges. The theoretical methods are used. The bilayer electrostriction induced by the electric field in the presence of intramembrane charges is computed. The intramembrane field depends upon localisation of the charges inside the bilayer like a sine curve; it goes to zero if the charges are located in the centre of the membrane. The charge discreteness affects the value of the compensation voltage due to nonlinearity of the bilayer deformations close to the charge. The probable appendices of outcomes are discussed for problems of intramembrane dye localisation and ion transport in the channel of sodium/potassium ATPase.     

Electrochemical investigation of melittin reconstituted into a mercury-supported lipid bilayer

The channel-forming peptide melittin was incorporated into a biomimetic membrane consisting of a mercury electrode coated with a thiolipid monolayer, with a lipid monolayer self-assembled on top of it. The thiolipid consisted of a hydrophilic tetraethyleneoxy chain terminated at one end with a disulfide group, for anchoring to the mercury surface, and covalently linked at the other end to two diphytanyl chains, which formed a lipid bilayer with the overhanging lipid monolayer. The conductance of the lipid bilayer in contact with aqueous 0.1 M KCl was measured by electrochemical impedance spectroscopy over a frequency range from 1 x 10(-2) to 1 x 10(5) Hz and a potential range of 0.7 V for different compositions of the outer lipid monolayer. The conductance increases abruptly above the background level at sufficiently negative applied potentials, attaining a maximum value that increases with the composition of the outer monolayer in the order PC/chol (60:40) < PC < PC/SM/chol (59:15:26) < PS, with PC = phosphatidylcholine, chol = cholesterol, SM = sphingomyelin, and PS = phosphatidylserine. The higher the maximum conductance, the less negative the applied potential at which it is attained. This behavior is also discussed using a model of the electrified interphase.     

Water solvent and local anesthetics: A computational study

There are various experimental studies regarding the toxicity and the time of action of local anesthetics, which contain general insights about their pharmacological and physicochemical properties. Although a detailed microscopic analysis of the local anesthetics would contribute to understanding these properties, there are relatively few theoretical studies about these molecules. In this article, we present the results from calculations performed for three local anesthetics: tetracaine, procaine, and lidocaine, both in their charged and uncharged forms, in aqueous environment. We have used the density functional theory and molecular dynamics simulations to study the structural characteristics of these compounds. The radial distribution function g(r) was used to examine the structure of water molecules surrounding different regions of the local anesthetics. We demonstrated the nonhomogeneous character of the anesthetics with respect to their affinity to water solvent molecules as well as the modifications in their affinity to water caused by changes in their charge state. We also observed that the biological potency of the anesthetics is more related to the behavior of specific groups within the molecule, which are responsible for the interaction with the lipid phase of membranes, rather than the general properties of the molecule as a whole. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Glyco-acrylate copolymers for bilayer tethering on benzophenone-modified substrates

Model biological membranes are becoming increasingly important for studying fundamental biophysical phenomena and developing membrane-based devices. To address the anticipated problem of non-physiological interactions between membrane proteins and substrates seen in “solid-supported lipid bilayers” that are formed directly on hydrophilic substrates, we have developed a polymer-tethered lipid bilayer system based on a random copolymer with multiple lipid analogue anchors and a glyco-acrylate backbone. This system is targeted at applications that, most importantly, require stability and robustness since each copolymer has multiple lipid analogues that insert into the bilayer. We have combined this copolymer with a flexible photochemical coupling scheme that covalently attaches the copolymer to the substrate. The Langmuir isotherms of mixed copolymer/free lipid monolayers measured at the air–water interface indicate that the alkyl chains of the copolymer lipid analogues and the free lipids dominate the film behavior. In addition, no significant phase transitions are seen in the isotherms, while hysteresis experiments confirm that no irreversible states are formed during the monolayer compression. Isobaric creep experiments at the air–water interface and AFM experiments of the transferred monolayer are used to guide processing parameters for creating a fluid, homogeneous bilayer. Bilayer homogeneity and fluidity are monitored using fluorescence microscopy. Continuous bilayers with lateral diffusion coefficients of 0.6 μm²/s for both leaflets of the bilayer are observed for a 5% copolymer system.     

Formation and finite element analysis of tethered bilayer lipid structures

Rapid solvent exchange of an ethanolic solution of diphytanoyl phosphatidylcholine (DPhyPC) in the presence of a mixed self-assembled monolayer (SAM) [thiolipid/β-mercaptoethanol (βME) (3/7 mol/mol) on Au] shows a transition from densely packed tethered bilayer lipid membranes [(dp)tBLMs], to loosely packed tethered bilayer lipid membranes [(lp)tBLMs], and tethered bilayer liposome nanoparticles (tBLNs) with decreasing DPhyPC concentration. The tethered lipidic constructs in the aqueous medium were analyzed by atomic force microscopy (AFM) and electrochemical impedance spectroscopy (EIS). Finite element analysis (FEA) was applied to interpret spectral EIS features without referring to equivalent circuit modeling. Using structural data obtained earlier from neutron reflectometry and dielectric constants of lipid bilayers, we reproduced experimentally observed features of the electrochemical impedance (EI) spectra of complex surface constructs involving small pinhole defects, large membrane-free patches, and bound liposomes. We demonstrated by FEA that highly insulating (dp)tBLMs with low-defect density exhibit EI spectra in the shape of a perfect semicircle with or without low-frequency upward "tails" in the Cole-Cole representation. Such EI spectra were observed at DPhyPC concentrations of >5 × 10(-3) mol L(-1). While AFM was not able to visualize very small lateral defects in such films, EI spectra unambiguously signaled their presence by increased low frequency "tails". Using FEA we demonstrate that films with large diameter visible defects (>25 nm by AFM) produce EI spectral features consisting of two semicircles of comparable size. Such films were typically obtained at DPhyPC concentrations of <5 × 10(-3) mol L(-1). At DPhyPC concentrations of <1.0 × 10(-3) mol L(-1) the planar bilayer structures were replaced by ellipsoidal liposomes with diameters ranging from 50 to 500 nm as observed in AFM images. Despite the distinct surface morphology change, the EI curves exhibited two semicircle spectral features typical for the large size defects in planar tBLMs. FEA revealed that, to account for these EI features for bound liposome systems (50-500 nm diameter), one needs to assume much lower tBLM conductivities of the submembrane space, which separates the electrode surface and the phospholipid bilayer. Alternatively, FEA indicates that such features may also be observed on composite surfaces containing both bound liposomes and patches of planar bilayers. Triple semicircular features, observed in some of the experimental EI curves, were attributed to an increased complexity of the real tBLMs. The modeling demonstrated that such features are typical for heterogeneous tBLM surfaces containing large patches of different defectiveness levels. By integrating AFM, EIS, and FEA data, our work provides diagnostic criteria allowing the precise characterization of the properties and the morphology of surface supported bilayer systems.     

Influence of inhalation anesthetics on ion transport across a planar bilayer lipid membrane

Ion transport from one aqueous phase (W1) to another (W2) across a planar bilayer lipid membrane (BLM) in the presence of inhalation anesthetics was electrochemically investigated. In the absence of inhalation anesthetics in the BLM system, no ion transport current flowed between W1 and W2 across the BLM. When inhalation anesthetics such as halothane, chloroform, diethyl ether and trichloroethylene were added to the two aqueous phases or the BLM, the ion transport current quite clearly appeared. When the ratio of the concentration of KCl or NaCl in W1 to that in W2 was varied, the zero current potential across the BLM was shifted. By considering the magnitude of the potential shift, we concluded that the ion transport current can be predominantly ascribed to the transport of Cl(-) across the BLM. Since the dielectric constants of these anesthetics are larger than that of the inner hydrophobic domain of the BLM, the concentration of hydrophilic electrolyte ions in the BLM increases with the increase in the dielectric constant of the inner hydrophobic domain caused by addition of these anesthetics. These situations lead to an increase in the ion permeability coefficient.     

A facile approach for assembling lipid bilayer membranes on template-stripped gold

Lipid vesicles are designed with functional chemical groups to promote vesicle fusion on template-stripped gold (TS Au) surfaces that does not spontaneously occur on unfunctionalized Au surfaces. Three types of vesicles were exposed to TS Au surfaces: (1) vesicles composed of only 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids; (2) vesicles composed of lipid mixtures of 2.5 mol % of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-poly(ethylene glycol)-2000-N-[3-(2-pyridyldithio)propionate] (DSPE-PEG-PDP) and 97.5 mol % of POPC; and (3) vesicles composed of 2.5 mol % of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG) and 97.5 mol % POPC. Atomic force microscopy (AFM) topography and force spectroscopy measurements acquired in a fluid environment confirmed tethered lipid bilayer membrane (tLBM) formation only for vesicles composed of 2.5 mol % DSPE-PEG-PDP/97.5 mol % POPC, thus indicating that the sulfur-containing PDP group is necessary to achieve tLBM formation on TS Au via Au-thiolate bonds. Analysis of force-distance curves for 2.5 mol % DSPE-PEG-PDP/97.5 mol % POPC tLBMs on TS Au yielded a breakthrough distance of 4.8 ± 0.4 nm, which is about 1.7 nm thicker than that of POPC lipid bilayer membrane formed on mica. Thus, the PEG group serves as a spacer layer between the tLBM and the TS Au surface. Fluorescence microscopy results indicate that these tLBMs also have greater mechanical stability than solid-supported lipid bilayer membranes made from the same vesicles on mica. The described process for assembling stable tLBMs on Au surfaces is compatible with microdispensing used in array fabrication.