Condensing effect of palmitic acid on DPPC in mixed Langmuir monolayers

The interaction between deuterated dipalmitoylphosphatidylcholine (DPPC-d62) and palmitic acid (PA) in mixed Langmuir monolayers is studied using vibrational sum frequency generation (VSFG) spectroscopy. Palmitic acid is an additive in exogenous lung surfactant preparations such as Survanta and Surfaxin. The effect of PA on the chain conformation and orientation of DPPC in the liquid-expanded and condensed phases is explored. A condensing effect of PA on DPPC is observed with VSFG. At 12 mN/m, DPPC-d62 alone is in the liquid-expanded phase. Adding PA increases the conformational ordering of DPPC chains and causes DPPC to transition from the expanded phase into the condensed phase. At 42 mN/m, DPPC-d62 and PA form a mixed structure in the condensed phase. The presence of PA decreases the chain tilt angle of DPPC, increasing the orientational ordering of DPPC chains. At 42 mN/m, there is also evidence from the frequency red shift of the PO2- symmetric stretch that the carboxyl group of PA forms a hydrogen bond with the phosphate group of DPPC in the condensed phase. From this work the effect of PA on DPPC is 2-fold: (1) PA increases the chain ordering of DPPC and promotes the LE and TC phase separation and (2) due to the miscibility between DPPC and PA in the condensed phase, PA decreases the collapse pressure.     

Influence of a fluorescent probe on the nanostructure of phospholipid membranes: dipalmitoylphosphatidylcholine interfacial monolayers

Monolayers of dipalmitoylphosphatidylcholine (DPPC), both in the absence and in the presence of 1% (mol/mol) of a fluorescent phospholipid probe, have been spread at the air-liquid interface of a surface balance, compressed up to pressures in the liquid-expanded/liquid-condensed plateau of the isotherm, transferred onto mica supports, and analyzed by scanning force microscopy (SFM). Supported DPPC films showed micrometer-sized condensed domains with morphology and size that were entirely analogous to those observed in situ at the air-liquid interface by epifluorescence microscopy. The analysis by SFM, however, allowed the study and comparison of monolayers in the absence and in the presence of the fluorescent marker. This analysis revealed that the presence of dye reduced by 10-20% the total amount of the liquid-condensed phase in the DPPC films. The presence of the dye also decreased the mechanical stability of the film and increased the time required for the monolayer to equilibrate. The resolution of SFM permitted the determination that the structures of both the liquid-expanded and the liquid-condensed regions of DPPC films were heterogeneous at the nanometer scale. Liquid-condensed DPPC microdomains contained nanoholes covering 4-8% of their area whereas 60-80% of the surface detected as liquid-expanded by fluorescence microscopy consisted of a condensed-like framework of nanodomains. The total area, the shape of the nanodomains, and their interconnectivity were affected by the presence of the probe, suggesting that care must be taken when studying the structure, especially at the nanometer scale, and properties of model lipid films in the presence of extrinsic probes.     

Molecular interactions of cord factor with dipalmitoylphosphatidylcholine monolayers: implications for lung surfactant dysfunction in pulmonary tuberculosis

Molecular interactions between mycobacterial cell wall lipid, cord factor (CF) and the abundant surfactant lipid, dipalmitoylphosphatidylcholine (DPPC) were investigated using Langmuir monolayers at physiological temperatures (37 degrees C). Surface topography of the films was visualized by atomic force microscopy (AFM). Thermodynamic behavior of the mixed monolayers was evaluated by investigating the molecular area excess, excess Gibbs free energy of mixing and maximum compressibility modulus (SCM(max)). Cord factor formed immiscible and thermodynamically unstable monolayers with DPPC. Monolayer presence of cord factor altered the physical state of DPPC monolayers from liquid condensed to liquid expanded with the lowering of SCM(max) from 160 to 40 mN/m, respectively. AFM imaging exhibited smooth homogenous surface topography of DPPC films which in the presence of cord factor was markedly altered with the appearance of aggregates and increased surface roughness. The results highlight the capacity of cord factor to disturb DPPC monolayer organization and structure. Interfacial presence of cord factor results in DPPC monolayer fluidization. Lung surfactant function is attributed to its ability to form well packed low compressibility films. Such molecular interactions suggest a dysfunction of lung surfactant in pulmonary tuberculosis due to surfactant monolayer fluidization.     

Effect of hydrocarbon chain and pH on structural and topographical characteristics of phospholipid monolayers

Structural characteristics (structure, elasticity, topography, and film thickness) of dipalmitoyl phosphatidylcholine (DPPC) and dioleoyl phosphatidylcholine (DOPC) monolayers were determined at the air-water interface at 20 degrees C and pH values of 5, 7, and 9 by means of surface pressure (pi)-area (A) isotherms combined with Brewster angle microscopy (BAM) and atomic force microscopy (AFM). From the pi-A isotherms and the monolayer elasticity, we deduced that, during compression, DPPC monolayers present a structural polymorphism at the air-water interface, with the homogeneous liquid-expanded (LE) structure; the liquid-condensed structure (LC) showing film anisotropy and DPPC domains with heterogeneous structures; and, finally, a homogeneous structure when the close-packed film molecules were in the solid (S) structure at higher surface pressures. However, DOPC monolayers had a liquid-expanded (LE) structure under all experimental conditions, a consequence of weak molecular interactions because of the double bond of the hydrocarbon chain. DPPC and DOPC monolayer structures are practically the same at pH values of 5 and 7, but a more expanded structure in the monolayer with a lower elasticity was observed at pH 9. BAM and AFM images corroborate, at the microscopic and nanoscopic levels, respectively, the same structural polymorphism deduced from the pi-A isotherm for DPPC and the homogeneous structure for DOPC monolayers as a function of surface pressure and the aqueous-phase pH. The results also corroborate that the structural characteristics and topography of phospholipids (DPPC and DOPC) are highly dependent on the presence of a double bond in the hydrocarbon chain.     

Infrared reflection absorption spectroscopy coupled with Brewster angle microscopy for studying interactions of amphiphilic triblock copolymers with phospholipid monolayers

Novel water-soluble amphiphilic triblock copolymers poly(glycerol monomethacrylate)-b-poly(propylene oxide)-b-poly(glycerol monomethacrylate) (PGMA-b-PPO-b-PGMA) were synthesized because of their expected enhanced ability to interact with biological membranes compared to the well-known poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-b-PPO-b-PEO) block copolymers. Their bulkier hydrophilic PGMA blocks might induce a disturbance in the packing of liquid-crystalline lipid bilayers in addition to the effect caused by the hydrophobic PPO block alone. To gain a better insight into the polymer-membrane interactions at the molecular level, the adsorption kinetics and concomitant interactions of (PGMA14)(2-)PPO(34) with model membranes of dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) were monitored using infrared reflection absorption spectroscopy (IRRAS) coupled with Brewster angle microscopy (BAM) and surface pressure (pi) measurements. The maximum penetration surface pressure of ca. 39 mN/m suggests that (PGMA14)(2-)PPO(34) is able to insert into lipid monolayers even above the so-called monolayer-bilayer equivalent pressure of 30-35 mN/m. Copolymer adsorption to a liquid-expanded DPPC-d62 monolayer proceeds in a two-step mechanism: (i) initially only the more hydrophobic PPO middle block penetrates the lipid monolayer; (ii) following the liquid-expanded-liquid-condensed (LE-LC) phase transition, the bulky PGMA hydrophilic blocks are dragged into the headgroup region as the PPO block inserts further into the fatty acid region. The adsorption kinetics is considerably faster for DMPC-d54 monolayers due to their higher fluidity. Copolymer adsorption to an LC-DPPC-d62 monolayer leads to a change in the monolayer packing by forcing the lipid alkyl chains into a more vertical orientation, their tilt angle with respect to the surface normal being reduced from initially 30 degrees +/- 3 degrees to 18 degrees +/- 3 degrees. BAM images rule out macroscopic phase separation and show that coalescence of DPPC-d62 LC domains takes place at relatively low surface pressures of pi > or = 23 mN/m, suggesting that (PGMA14)(2-)PPO (34) partitions into both LE as well as LC domains.     

A monolayer study on interactions of docetaxel with model lipid membranes

Docetaxel (DCT) is an antineoplastic drug for the treatment of a wide spectrum of cancers. DCT surface properties as well as miscibility studies with l-alpha-dipalmitoyl phosphatidylcholine (DPPC), which constitutes the main component of biological membranes, are comprehensively described in this contribution. Penetration studies have revealed that when DCT is injected under DPPC monolayers compressed to different surface pressures, it penetrates into the lipid monolayer promoting an increase in the surface pressure. DCT is a surface active molecule able to decrease the surface tension of water and to form insoluble films when spread on aqueous subphases. The maximum surface pressure reached after compression of a DCT Langmuir film was 13 mN/m. Miscibility of DPPC and DCT in Langmuir films has been studied by means of thermodynamic properties as well as by Brewster angle microscopy (BAM) analysis of the mixed films at the air-water interface, concluding that DPPC and DCT are miscible and they form non-ideally mixed monolayers at the air-water interface. Helmholtz energies of mixing revealed that no phase separation occurs. In addition, Helmholtz energies of mixing become more negative with decreasing areas per molecule, which suggests that the stability of the mixed monolayers increases as the monolayers become more condensed. Compressibility values together with BAM images indicate that DCT has a fluidizing effect on DPPC monolayers.     

Mixing behavior of 10-(perfluorohexyl)-decanol and DPPC

Fluorocarbon alcohol such as 10-(perfluorohexyl)-decanol are of interest for novel pulmonary drug delivery approaches. The purpose of this study was to investigate the mixing behavior of 10-(perfluorohexyl)-decanol with dipalmitoylphosphatidylcholine (DPPC), the major component of lung surfactant as an aid in assessing usefulness for this and other biomedical applications. The impact of 10-(perfluorohexyl)-decanol on the phase transitions of DPPC bilayers fully hydrated with a 0.15 M sodium chloride solution were studied using differential scanning calorimetry (DSC). No peak corresponding to excess alcohol was observed. The fluorinated alcohol caused DPPC peak broadening, especially below X(DPPC) < 0.95, and elimination of the pretransition of DPPC at X(DPPC) approximately 0.91. The onset of the main phase transition remains constant down to X(DPPC) approximately 0.91, suggesting limited miscibility in the gel phase. Hydration of the 10-(perfluorohexyl)-decanol-DPPC mixtures with calcium chloride (2 mM) in place of sodium chloride did not alter the macroscopic phase behavior. In addition to the thermal properties, the miscibility of 10-(perfluorohexyl)-decanol in DPPC in monolayers at the air water interface was investigated on water, sodium chloride (0.15 M), calcium chloride (2 mM) or hydrochloric acid (pH 1.9) subphases. The concentration dependence of the onset pressure of the liquid-expanded to liquid condensed phase transition of DPPC showed a slight change with increasing mole fraction on all four subphases. The surface area-mole fraction diagrams of 10-(perfluorohexyl)-decanol and DPPC on water, sodium chloride and calcium chloride showed near ideal behavior with slight negative deviations at higher surface pressure. A more significant negative deviation was observed for the hydrochloric acid subphase. Overall, both the DSC and the monolayer studies suggest that 10-(perfluorohexyl)-decanol and DPPC are partially miscible in biological mono- and bilayers. The macroscopic phase behavior 10-(perfluorohexyl)-decanol-DPPC system is significantly different from the analogous hydrocarbon system, which is attributed to a less favorable packing of the partially fluorinated hydrophobic tails in the mono- and bilayer.     

RNA and DNA association to zwitterionic and charged monolayers at the air-liquid interface

The objective of this work is to establish under which conditions short RNA molecules (similar to miRNA) associate with zwitterionic phospholipids and how this differs from the association with cationic surfactants. We study how the base pairing (i.e., single stranded versus double stranded nucleic acids) and the length of the nucleic acid and the charge of the lipid/surfactant monolayer affect the association behavior. For this purpose, we study the adsorption of nucleic acids to monolayers composed of dipalmitoyl phosphatidylcholine (DPPC) or dioctadecyl-dimethyl-ammoniumbromide (DODAB) using the surface film balance, neutron reflectometry, and fluorescence microscopy. The monolayer studies with the surface film balance suggested that short single-stranded ssRNA associates with liquid expanded zwitterionic phospholipid monolayers, whereas less or no association is detected for double-stranded dsRNA and dsDNA. In order to quantify the interaction and to determine the location of the nucleic acid in the lipid/surfactant monolayer we performed neutron reflectometry measurements. It was shown that ssRNA adsorbs to and penetrates the liquid expanded monolayers, whereas there is no penetration of nucleic acids into the liquid condensed monolayer. No adsorption was detected for dsDNA to zwitterionic monolayers. On the basis of these results, we propose that the association is driven by the hydrophobic interactions between the exposed hydrophobic bases of the ssRNA and the hydrocarbon chains of the phospholipids. The addition of ssRNA also influences domain formation in the DPPC monolayer, leading to fractal-like interconnected domains. The experimental results are discussed in terms of the implication for biological processes and new leads for applications in medicine and biotechnology.     

Dynamic tension and adsorption behavior of aqueous lung surfactants

The dynamic tension behavior, at constant or at pulsating area conditions, of two commercial lung surfactants in saline is reported. The bubble method, at constant or pulsating area, at 37°C and the pendant drop method at 23°C were used. For Exosurf, a commercial synthetic lung surfactant consisting of dissolved tyloxapol and dispersed dipalmitoylphosphatidylcholine (or DPPC) and hexadecanol (H), the equilibrium and dynamic tensions are high (over 30 mN m⁻¹) and similar to those of tyloxapol alone. Aqueous DPPC/H mixtures have lower tensions than Exosurf. Survanta, a commercial lung surfactant replacement drug consisting of DPPC, other lipids, and two hydrophobic lung surfactant proteins, produces dynamic surface tensions that are substantially lower than those of Exosurf. Diluted 10-fold, Survanta produces under pulsating area (at 20 cycles min⁻¹) lower minimum tensions than undiluted Survanta (6 vs. 12 mN m⁻¹), but higher maximum tensions. In addition, Survanta tension behavior is unusual, having three local maxima and three local minima per cycle, suggesting major variations of its surface composition in each cycle. Monolayer pressure-area isotherms and Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy results on deposited Langmuir–Blodgett films support this suggestion. They also provide direct evidence of the presence of phospholipids (DPPC or others) on the surface, but only indirect evidence of the presence of other components, on the surface of aqueous Exosurf or Survanta.     

Effect of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on surfactant monolayers

In the present study, the effects of an amphiphilic polymer, d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on model surfactant monolayers dipalmitoylphosphatidylcholine (DPPC), a binary mixture of DPPC with palmitoyloleoyl phosphatidylglycerol (DPPC-POPG) 9:1 (w/w) and binary mixture of DPPC and oleic acid (DPPC-OA) were evaluated. The ability of TPGS to act as an antioxidant adjuvant for pulmonary surfactants was also evaluated. Compression isotherms of surfactant monolayers at 37 °C in a Langmuir-Blodgett trough showed that DPPC and DPPC:TPGS mixed monolayers (1:0.25-1:1, w/w) exhibited low minimum surface tensions (MST) of 1-2 mN/m. Similarly [DPPC:POPG (9:1, w/w)]:TPGS mixed films of 1:0.25-1:1 weight ratios reached 1-2 mN/m MST. DPPC:POPG:TPGS liposomes adsorbed to surface tensions of 29-31 mN/m within 1s. While monolayers of DPPC:OA (1:1, w/w) reached high MST of ～11 mN/m, DPPC:OA:TPGS (1:1:0.25, w/w) film reached near zero MST suggesting that low concentrations of TPGS reverses the effect of OA on DPPC monolayer. Capillary surfactometer studies showed DPPC:TPGS and [DPPC:POPG (9:1, w/w)]:TPGS liposomes maintained 84-95% airway patency. Fluorescence spectroscopy of Laurdan loaded DPPC:TPGS and DPPC:POPG:TPGS liposomes revealed no segregation of lipid domains in the lipid bilayer. Addition of TPGS to soybean liposome significantly reduced thiobarbituric acid reactive substance (TBARS) by 29-39% confirming its antioxidant nature. The results suggest a potential use of TPGS as an adjuvant to improve the surfactant activity as well as act as an antioxidant by scavenging free radicals.     

Penetration of dissolved amphiphiles into two-dimensional aggregating lipid monolayers

The review demonstrates the recent theoretical and experimental progress in the understanding of penetration systems at the air-water interface in which a dissolved amphiphile (surfactant, protein) penetrates into a Langmuir monolayer. The critical review of the existing theoretical models which describe the thermodynamics of the penetration are critically reviewed. Although a rigorous thermodynamic analysis of penetration systems is unavailable due to their complexity, some model assumptions, e.g. the invariability of the activity coefficient of the insoluble component of the monolayer during the penetration of the soluble component results in reasonable solutions. New theoretical models describing the equilibrium behaviour of the insoluble monolayers which undergo the 2D aggregation in the monolayer, and the equations of state and adsorption isotherms which assume the existence of multiple states (conformations) of a protein molecule within the monolayer and the non-ideality of the adsorbed monolayers are now available. The theories which describe the penetration of a soluble surfactant into the main phases of Langmuir monolayers were presented first for the case of the mixture of the molecules possessing equal partial molar surfaces (the mixture of homologues), with further extension of the models to include the interesting process of the protein penetration into the monolayer of 2D aggregating phospholipid. This extension was based on a concept which subdivides the protein molecules into independent fragments with areas equal to those of the phospholipid molecule. Various mechanisms for the effect of the soluble surfactant on the aggregation of the insoluble component were considered in the theoretical models: (i) no effect on the aggregate formation process; (ii) formation of mixed aggregates; and (iii) the influence on the aggregating process via the change of aggregation constant, but without any formation of mixed aggregates. Accordingly depending on the mechanism, different forms of the equations of state of the monolayer and of the adsorption isotherms of soluble surfactant are predicted. Based on the shape of the experimental pi-A isotherms, interesting conclusions can be drawn on the real mechanism. First experimental evidence has been provided that the penetration of different proteins and surfactants into a DPPC monolayer in a fluid-like state induces a first order main phase transition of pure DPPC. The phase transition is indicated by a break point in the pi(t) penetration kinetics curves and the domain formation by BAM. Mixed aggregates of protein with phospholipid are not formed. These results agree satisfactorily with the predictions of the theoretical models. New information on phase transition and phase properties of Langmuir monolayers penetrated by soluble amphiphiles are obtained by coupling of the pi(t) penetration kinetics curves with BAM and GIXD measurements. The GIXD results on the penetration of beta-lactoglobulin into DPPC monolayers have shown that protein penetration occurs without any specific interactions with the DPPC molecules and the condensed phase consists only of DPPC.     

Temperature dependent dendritic domain shapes in Langmuir monolayers of tetradecanoyl N-ethanolamide at the air-water interface

The effect of temperature on the surface phase behavior of tetradecanoyl N-ethanolamide (NHEA-14) in Langmuir monolayers at the air-water interface has been investigated by film balance and Brewster angle microscopy (BAM). It has been observed that dendritic domains are formed in the coexistence region between liquid-expanded (LE) and liquid-condensed (LC) phases at different temperatures. At 10 and 15°C, the domains are four-armed dendrites having wide arms which have a tendency to be fractal while growing in size. At 20°C, five-armed dendritic domains are formed. At a temperature higher than 20°C, the domains are mainly six-armed dendrites having very narrow and sharp arms. The formation of dendritic domains should be due to the presence of interfacial hydrogen bonding among the head groups of the amphiphile. Increased dehydration of the head groups with an increase in the temperature should be responsible for the temperature dependency of the dendritic domain shapes in the monolayers of NHEA-14.     

Effects of albumin and erythrocyte membranes on spread monolayers of lung surfactant lipids

Dipalmitoyl phosphatidylcholine (DPPC), one of the main constituents of lung surfactant is mainly responsible for reduction of surface tension to near 0 mN/m during expiration, resisting alveolar collapse. Other unsaturated phospholipids like palmitoyloleoyl phosphatidylglycerol (PG), palmitoyloleoyl phosphatidylcholine (POPC) and neutral lipids help in adsorption of lung surfactant to the air-aqueous interface. Lung surfactant lipids may interact with plasma proteins and hematological agents flooding the alveoli in diseased states. In this study, we evaluated the effects of albumin and erythrocyte membranes on spread films of DPPC alone and mixtures of DPPC with each of PG, POPC, palmitoyloleoyl phosphatidylethanolamine (PE), cholesterol (CHOL) and palmitic acid (PA) in 9:1 molar ratios. Surface tension-area isotherms were recorded using a Langmuir-Blodgett (LB) trough at 37 degrees C with 0.9% saline as the sub-phase. In the presence of erythrocyte membranes, DPPC and DPPC+PA monolayers reached minimum surface tensions of 7.3+/-0.9 and 9.6+/-1.4 mN/m, respectively. Other lipid combinations reached significantly higher minimum surface tensions >18 mN/m in presence of membranes (Newman Keul's test, p<0.05). The relative susceptibility to membrane inhibition was [(DPPC+PG, 7:3)=(DPPC+PG, 9:1)=(DPPC+POPC)=(DPPC+PE)=(DPPC+CHOL)]>[(DPPC+PA)=(DPPC)]. The differential response was more pronounced in case of albumin with DPPC and DPPC+PA monolayers reaching minimum surface tensions less than 2.4 mN/m in presence of albumin, whereas DPPC+PG and DPPC+POPC reached minimum surface tensions of around 20 mN/m in presence of albumin. Descending order of susceptibility of the spread monolayers of lipid mixtures to albumin destabilization was as follows: [(DPPC+PG, 7:3)=(DPPC+PG, 9:1)=(DPPC+POPC)]>[(DPPC+PE)=(DPPC+CHOL)]>[(DPPC+PA)=(DPPC)] The increase in minimum surface tension in presence of albumin and erythrocyte membranes was accompanied by sudden increases in compressibility at surface tensions of 15-30 mN/m. This suggests a monolayer destabilization and could be indicative of phase transitions in the mixed lipid films due to the presence of the hydrophobic constituents of erythrocyte membranes.     

Externally applied electric fields on immiscible lipid monolayers: repulsion between condensed domains precludes domain migration

Lipid and protein molecules anisotropically oriented at a hydrocarbon-aqueous interface configure a dynamic array of self-organized molecular dipoles. Electrostatic fields applied to lipid monolayers have been shown to induce in-plane migration of domains or phase separation in a homogeneous system. In this work, we have investigated the effect of externally applied electrostatic fields on different lipid monolayers exhibiting surface immiscibility. In the monolayers studied, lipids in the condensed state segregate in discontinuous round-shaped domains, with the lipid in the liquid-expanded state forming the continuous phase. The use of fluorescent probes with selective phase partitioning allows analyzing by epifluorescence microscopy the migrations of the domains under the influence of inhomogeneous electric fields applied to the surface. Our observations indicate that a positive potential applied to an electrode placed over the monolayer promotes a repulsion of the domains until a steady state is reached, indicating the presence of a force opposed to the externally applied electric force. The experimental results were modeled by considering that the opposing force is generated by the dipole-dipole repulsion between the domains.     

The role of nonsurface-active species at interfacial molecular recognition by melamine-type monolayers

The main characteristics of Langmuir monolayers are radically changed by molecular recognition of hydrogen bond nonsurface-active species. The change in the thermodynamic, phase, and structural features by molecular recognition of dissolved uracil or barbituric acid by 2,4-di(n-undecylamino)-6-amino-1,3,5-triazine (2C11H23-melamine) monolayers is characterized by combination of surface pressure studies with Brewster angle microscopy (BAM) imaging and Grazing incidence X-ray diffraction (GIXD) measurements. Phase behavior of the 2C11H23-melamine monolayer and morphology of the condensed phase domains are changed drastically, but in a specific way, by molecular recognition of uracil or barbituric acid. The main characteristics of the interfacial system can be essentially affected by the kinetics of the recognition process. Pure 2C11H23-melamine monolayers show only small compact, but nontextured domains. The monolayers of 2C11H23-melamine-uracil assemblies develop well-shaped circular condensed-phase domains having an inner texture with alkyl chains essentially oriented parallel to the periphery and having a striking tendency to two-dimensional (2D) Ostwald ripening. The 2C11H23-melamine-barbituric acid monolayers form large homogeneous areas of condensed phase that transfer at smaller areas per molecule to a homogeneous condensed monolayer. BAM imaging of corresponding assemblies with ((CH3(CH2)11O(CH2)3)2-melamine having modified alkyl chains demonstrates the specific effect of the monolayer component. GIXD results reveal that molecular recognition of pyrimidine derivatives gives rise only to quantitative changes in the two-dimensional lattice structure. The striking differences in the main characteristics between the supramolecular species are related to their different chemical structures. Quantum chemical calculations using the semiempirical PM3 method provide information about the different nature of the hydrogen-bonding-based supramolecular structures.     

Negative dipole potentials of uncharged langmuir monolayers due to fluorination of the hydrophilic heads

The dipole potential, affecting the structure, functions, and interactions of biomembranes, lipid bilayers, and Langmuir monolayers, is positive toward the hydrocarbon moieties. We show that uncharged Langmuir monolayers of docosyl trifluoroethyl ether (DFEE) exhibit large negative dipole potentials, while the nonfluorinated docosyl ethyl ether (DEE) forms films with positive dipole potentials. Comparison of the Delta V values for these ethers with those of the previously studied(37-39) monolayers of trifluoroethyl ester (TFEB) and ethyl ester of behenic acid (EB) shows that the reversal of the sign of Delta V causes the same change Delta(Delta V) = -706 +/- 16 mV due to fluorination of heads. The Delta V values of both TFEB and EB films differ by -122 +/- 16 mV from those of DFEE and DEE monolayers, respectively, with the same density. Such quantitative coincidence points to a common mechanism of reversal of the sign of the dipole potential for the ether and ester films despite the different structure of their heads. The mechanical properties and phase behaviors of these monolayers show that both fluorinated heads are less hydrated, suggesting that the change of the sign of Delta V could, at least partially, be related to different hydration water structure. The same negative contribution of the carbonyl bond in both TFEB and EB films contrasts with the generally accepted positive contribution of the C(delta+)=O(delta-) bond in condensed Langmuir monolayers of fatty acids, their alcohol esters, glycerides, and phospholipids but concurs with the theoretical analysis of Delta V of stearic acid monolayers. Both results question the literature values of the molecular dipole moments of these substances calculated via summation of bonds and atomic group contributions. Mixed monolayers of DFEE and DEE show smooth monotonic variation of Delta V from +450 to -235 mV, indicating a way for adjustment of the sign and magnitude of the dipole potential at the membrane-water boundary and regulation of such membrane behaviors as binding and translocation rate of hydrophobic ions and ion-carriers, adsorption and penetration of amphiphilic peptides, polarization of hydration water, and short-range repulsion. The interaction of the hydrophobic ions tetraphenylboron TPhB- and tetraphenylphosphonium TPhP+ with DFEE and DEE monolayers qualitatively follows the theory of binding of such ions to lipid bilayers, but the shifts Delta(Delta V) from the values obtained on water are much smaller than those for DPPC monolayers. This difference seems to be due to the solid (polycrystalline) character of the DFEE and DEE films that hampers the penetration of TPhB- and TPhP+ in the monolayers and reduces the attractive interaction with the hydrophobic moiety. This conclusion orients the future synthesis of amphiphiles with fluorinated heads to those which could form liquid-expanded Langmuir monolayers.     

Insertion mechanism of a poly(ethylene oxide)-poly(butylene oxide) block copolymer into a DPPC monolayer

Interactions between amphiphilic block copolymers and lipids are of medical interest for applications such as drug delivery and the restoration of damaged cell membranes. A series of monodisperse poly(ethylene oxide)-poly(butylene oxide) (EOBO) block copolymers were obtained with two ratios of hydrophilic/hydrophobic block lengths. We have explored the surface activity of EOBO at a clean interface and under 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayers as a simple cell membrane model. At the same subphase concentration, EOBO achieved higher equilibrium surface pressures under DPPC compared to a bare interface, and the surface activity was improved with longer poly(butylene oxide) blocks. Further investigation of the DPPC/EOBO monolayers showed that combined films exhibited similar surface rheology compared to pure DPPC at the same surface pressures. DPPC/EOBO phase separation was observed in fluorescently doped monolayers, and within the liquid-expanded liquid-condensed coexistence region for DPPC, EOBO did not drastically alter the liquid-condensed domain shapes. Grazing incidence X-ray diffraction (GIXD) and X-ray reflectivity (XRR) quantitatively confirmed that the lattice spacings and tilt of DPPC in lipid-rich regions of the monolayer were nearly equivalent to those of a pure DPPC monolayer at the same surface pressures.     

Anomalous phase behavior in Langmuir monolayers of monomyristoyl-rac-glycerol at the air-water interface

The effect of temperature on the surface phase behavior in Langmuir monolayers of monomyristoyl-rac-glycerol (MMG) at the air-water interface has been studied by film balance and Brewster angle microscopy (BAM). It is observed that the domains of the MMG monolayers formed in the coexistence region between the liquid expanded (LE) and liquid condensed (LC) phases retain their circular shape over the studied temperature range, showing a sharp contrast to the temperature-dependent monolayer morphologies of amphiphilic systems where the shape of condensed domains changes either from compact circular to fingering or from irregular or spiral to compact patterns with increasing temperature. It is concluded that the system is capable of tuning the line tension of the interface by the effect of the increase in the hydrophobic character because of dehydration of the headgroup, which imparts to the molecules the properties of similar molecules but with less hydrophilic headgroups. As a result, the domains can retain their circular shape even up to the maximum possible temperature of the phase transition.