Mixtures containing a saturated phosphatidylcholine (PC)-lipid and polyethylene glycol (PEG)-lipid have been widely used in lipid bilayer and monolayer systems, in particular for forming drug delivery stealth liposomes and for stabilizing medical microbubble ultrasound contrast agents. The miscibility and phase behavior of these systems have been incompletely explored and controversial. Here, using complementary experimental methods and analysis, we examine the phase behavior and construct complete surface pressure (p)-composition phase diagrams for three binary Langmuir monolayer systems of increasing saturated PC-lipid chain-length from n ¼ 14 to n ¼ 18. Specifically, for DMPC, DPPC, and DSPC mixed with DSPE-PEG2000, we examine p-area per molecule isotherms, p-isothermal surface compressibility plots, molecular area-composition plots, and microstructure in fluorescent monolayers. We find that all three of these systems resembled different classical binary phase diagrams at 298K with the following notable phase behavior over wide ranges of composition and p: (1) DMPC/DSPE-PEG2000 forms a single condensed (C) phase containing a stoichiometric complex, DMPC 3 DSPE-PEG2000, in addition to a eutectic at X DSPE-PEG2000 z 0.66; (2) DPPC/DSPE-PEG2000 forms a single expanded (E) or C phase in addition to a peritectic at X DSPE-PEG2000 z 0.55; and, (3) DSPC/DSPE-PEG2000 displays two-phase coexistence where the two components are almost completely immiscible. The phase diagrams are used to elucidate previously unexplained or conflicting results in the literature and design principles of monolayers and bilayers for medical microbubbles and stealth liposomes. In addition, we suggest that these systems may be ideal models for testing mechanisms of lipid condensation by both experiment and theory.

In this letter, the long-term stabilization of monodisperse microbubbles produced by flow focusing is demonstrated using lipid encapsulation. Fluorescence microscopy, high-speed camera imaging, and particle size analysis were used to investigate the roles of lipid phase behavior, dissolution, Ostwald ripening, and coalescence in the stability of microbubbles formed by flow focusing. It was found that these behaviors were controlled through compositional changes with respect to lipid, emulsifier, and viscosity agents. Microbubbles coated with lipid and PEG emulsifier in a viscous solution were found to contain an extremely narrow size distribution (diameter av = 51 μm, standard deviation = 4 μm), which was maintained for up to several months.

Saturated diacyl (disaturated) phosphatidylcholine (PC) mixed with the lipopolymer distearoylphosphatidylethanolamine (DSPE)-polyethyleneglycol molecular weight 2000 (PEG2000) self-assemble as a monolayer at the air-water interface of air-in-water micrometer-scale bubbles (microbubbles), similar to coatings (shells) on leading medical ultrasound contrast agents (UCAs). This system is characterized here to study the impact of the DSPE-PEG2000 species and PC chain-length on the monolayer coating phase behavior, collapse, shedding, and air transport resistance and microbubble dissolution rate and surface contour. Using fluorescence microscopy of dissolving microbubbles, we found that film microstructure and collapse behavior for all chain lengths (n = 14-20) was indicative of primarily condensed phase monolayers, unlike similar coatings containing polyethyleneglycol 40 stearate (PEG40S) that are either expanded phase or coexisting expanded-condensed phase monolayers. Additionally, we observed a new surface buckling type of behavior with all chain lengths, by bright field microscopy, where the air-water interface continuously appears rough (rather than cyclically rough and smooth), with this behavior most frequently observed for n = 16. In correlating the statistical frequency of this behavior with the monolayer microstructure, we propose that it arises from a slowed nucleation rate of collapse structures at condensed-condensed phase interfaces, not present in systems containing PEG40S. By modeling the dissolution (radius vs time) data, we obtained, for each chain length, the film air transport resistance (R(shell)) that was then fit to a chain-length-dependent energy barrier model. Importantly, the pre-exponential factor was approximately 10 x higher and the microbubbles persisted approximately 4 x longer (from 15 microm at a fixed dissolved oxygen content) in comparison to previously studied films containing PEG40S. We attribute the unique stability properties of microbubble coatings containing DSPE-PEG2000 to the propensity of this molecule to form a condensed-phase monolayer, such that the monolayer coatings approach the properties of one continuous condensed domain.

The main objective of this study is to investigate the effect of resin I on the adsorption behavior of n-C 7 asphaltenes onto silica and hematite nanoparticles. It is worthwhile to mention, for the first time, that competitive adsorption of n-C 7 asphaltene and resin I over nanoparticles is reported. Indeed, a novel method based on thermogravimetric analysis (TGA) and softening point (SP) measurements was used for the simultaneously construction of adsorption isotherms of n-C 7 asphaltenes and resins. The adsorption experiments were conducted in the batch mode at different n-C 7 asphaltene to resin I (A:R) ratios of 7:3, 1:1, and 3:7 and different concentrations of the asphaltene−resin mixture from 500 mg/L to 5000 mg/L. The adsorption isotherms were described by the solid−liquid equilibrium (SLE) model. The results showed different shapes of the adsorption isotherms according to the A:R ratio. However, the nanoparticles become more selective for asphaltene at a high asphaltene/resin ratio. In addition, the amount of n-C 7 asphaltenes adsorbed at any of the A:R ratios evaluated was successfully predicted from a known amount adsorbed at a determined A:R ratio, following a simple rule of three. Results indicated that resin I does not have significant influence on the adsorbed amount of asphaltenes, showing that resin I has a solvent-like behavior, such as toluene, mainly at low concentrations (<3000 mg/L).

The characterization of the lateral organization of components in biological membranes and the evolution of this arrangement in response to external triggers remains a major challenge. The concept of lipid rafts is widely invoked, however, direct evidence of the existence of these ephemeral entities remains elusive. We report here the use of Secondary Ion Mass Spectrometry (SIMS) to image the cholesterol-dependent cohesive phase separation of the ganglioside GM1 into nano and micro-scale assemblies in a canonical lipid raft composition of lipids. This assembly of domains was interrogated in a model membrane system composed of palmitoyl sphingomyelin (PSM), cholesterol, and an unsaturated lipid (dioleoylphosphatidylcholine, DOPC). Orthogonal isotopic labeling of every lipid bilayer component and monofluorination of GM1 allowed generation of molecule specific images using a NanoSIMS. Simultaneous detection of six different ion species in SIMS, including secondary electrons, was used to generate ion ratio images whose signal intensity values could be correlated to composition through the use of calibration curves from standard samples. Images of this system provide the first direct, molecule specific, visual evidence for the co-localization of cholesterol and GM1 in supported lipid bilayers and further indicate the presence of three compositionally distinct phases: (1) the interdomain region; (2) micrometer-scale domains (d>3 μm); and, (3) nanometer-scale domains (d=100 nm − 1 μm) localized within the micrometer-scale domains and the interdomain region. PSM-rich, nanometer-scale domains prefer to partition within the more ordered, cholesterol-rich/DOPC-poor/GM1-rich micrometer-scale phase, while GM1-rich, nanometer-scale domains prefer to partition within the surrounding, disordered, cholesterol-poor/PSM-rich/DOPC-rich interdomain phase.