A concentration-dependent mechanism by which serum albumin inactivates replacement lung surfactants.

Endogenous lung surfactant, and lung surfactant replacements used to treat respiratory distress syndrome, can be inactivated during lung edema, most likely by serum proteins. Serum albumin shows a concentration-dependent surface pressure that can exceed the respreading pressure of collapsed monolayers in vitro. Under these conditions, the collapsed surfactant monolayer can not respread to cover the interface, leading to higher minimum surface tensions and alterations in isotherms and morphology. This is an unusual example of a blocked phase transition (collapsed to monolayer form) inhibiting bioactivity. The concentration-dependent surface activity of other common surfactant inhibitors including fibrinogen and lysolipids correlates well with their effectiveness as inhibitors. These results show that respreading pressure may be as important as the minimum surface tension in the design of replacement surfactants for respiratory distress syndrome.

The influence of polymer molecular weight in lamellar gels based on PEG-lipids.

We report x-ray scattering, rheological, and freeze-fracture and polarizing microscopy studies of a liquid crystalline hydrogel called Lalpha,g. The hydrogel, found in DMPC, pentanol, water, and PEG-DMPE mixtures, differs from traditional hydrogels, which require high MW polymer, are disordered, and gel only at polymer concentrations exceeding an "overlap" concentration. In contrast, the Lalpha,g uses very low-molecular-weight polymer-lipids (1212, 2689, and 5817 g/mole), shows lamellar order, and requires a lower PEG-DMPE concentration to gel as water concentration increases. Significantly, the Lalpha,g contains fluid membranes, unlike Lbeta' gels, which gel via chain ordering. A recent model of gelation in Lalpha phases predicts that polymer-lipids both promote and stabilize defects; these defects, resisting shear in all directions, then produce elasticity. We compare our observations to this model, with particular attention to the dependence of gelation on the PEG MW used. We also use x-ray lineshape analysis of scattering from samples spanning the fluid-gel transition to obtain the elasticity coefficients kappa and B; this analysis demonstrates that although B in particular depends strongly on PEG-DMPE concentration, gelation is uncorrelated to changes in membrane elasticity.

Lamellar biogels: fluid-membrane-based hydrogels containing polymer lipids.

A class of lamellar biological hydrogels comprised of fluid membranes of lipids and surfactants with small amounts of low molecular weight poly(ethylene glycol)-derived polymer lipids (PEG-lipids) were studied by x-ray diffraction, polarized light microscopy, and rheometry. In contrast to isotropic hydrogels of polymer networks, these membrane-based birefringent liquid crystalline biogels, labeled L-alpha,g, form the gel phase when water is added to the liquid-like lamellar L-alpha phase, which reenters a liquid-like mixed phase upon further dilution. Furthermore, gels with larger water content require less PEG-lipid to remain stable. Although concentrated (approximately 50 weight percent) mixtures of free PEG (molecular weight, 5000) and water do not gel, gelation does occur in mixtures containing as little as 0.5 weight percent PEG-lipid. A defining signature of the L-alpha,g regime as it sets in from the fluid lamellar L-alpha phase is the proliferation of layer-dislocation-type defects, which are stabilized by the segregation of PEG-lipids to the defect regions of high membrane curvature that connect the membranes.

A phase of liposomes with entangled tubular vesicles.

An equilibrium phase belonging to the family of bilayer liposomes in ternary mixtures of dimyristoylphosphatidylcholine (DMPC), water, and geraniol (a biological alcohol derived from oil-soluble vitamins that acts as a cosurfactant) has been identified. Electron and optical microscopy reveal the phase, labeled Ltv, to be composed of highly entangled tubular vesicles. In situ x-ray diffraction confirms that the tubule walls are multilamellar with the lipids in the chain-melted state. Macroscopic observations show that the Ltv phase coexists with the well-known L4 phase of spherical vesicles and a bulk L alpha phase. However, the defining characteristic of the Ltv phase is the Weissenberg rod climbing effect under shear, which results from its polymer-like entangled microstructure.

The X-ray Surface Forces Apparatus: Structure of a Thin Smectic Liquid Crystal Film Under Confinement.

An x-ray surface forces apparatus for simultaneously measuring forces and structures of confined complex fluids under static and flow conditions is described. This apparatus, combined with an intense synchrotron x-ray source, allows investigation of molecular orientations within a thin liquid crystal film confined between two shearing mica surfaces 3900 angstroms apart. The layer-forming smectic liquid crystal 8CB (4-cyano-4'-octylbiphenyl) adopted a series of distinct planar layer orientations, including the bulk flow-forbidden b orientation.