Biomedical subjects

Joseph A Zasadzinski

Publications and source records attributed to Joseph A Zasadzinski.

16 recordsLinked to original sources

PubMed2006

A brief review of the relationships between monolayer viscosity, phase behavior, surface pressure, and temperature using a simple monolayer viscometer.

The two-dimensional surface shear viscosity, eta, of fatty acid monolayers of different chain lengths, measured using a simple magnetic needle viscometer, strongly correlates with the molecular organization in condensed phases and the absolute temperature. eta can increase by orders of magnitude at phase boundaries associated with tilted to untilted molecular order, providing the underlying order is semicrystalline. Hence, untilted, long-range ordered CS phases are the most viscous films. However, despite being untilted, the LS rotator phase is less viscous than certain laterally ordered tilted phases, suggesting a decrease of the van der Waals interactions due to molecular rotation. In certain regions of the L2 phase, eta reaches a maximum before the L2-LS transition, an anomalous behavior correlated with the change in the lattice symmetry of the headgroup. Surface shear viscosity, even when measured with a macroscopic probe, is particularly sensitive to the microscopic organization of monolayers.

Fatty Acids↗

PubMed2006

Enhanced surfactant adsorption via polymer depletion forces: a simple model for reversing surfactant inhibition in acute respiratory distress syndrome.

Lung surfactant adsorption to an air-water interface is strongly inhibited by an energy barrier imposed by the competitive adsorption of albumin and other surface-active serum proteins that are present in the lung during acute respiratory distress syndrome. This reduction in surfactant adsorption results in an increased surface tension in the lung and an increase in the work of breathing. The reduction in surfactant adsorption is quantitatively described using a variation of the classical Smolukowski analysis of colloid stability. Albumin adsorbed to the interface induces an energy barrier to surfactant diffusion of order 5 k(B)T, leading to a reduction in adsorption equivalent to reducing the surfactant concentration by a factor of 100. Adding hydrophilic, nonadsorbing polymers such as polyethylene glycol to the subphase provides a depletion attraction between the surfactant aggregates and the interface that eliminates the energy barrier. Surfactant adsorption increases exponentially with polymer concentration as predicted by the simple Asakura and Oosawa model of depletion attraction. Depletion forces can likely be used to overcome barriers to adsorption at a variety of liquid-vapor and solid-liquid interfaces.

Adsorption↗

PubMed2006

Lamellar gels and spontaneous vesicles in catanionic surfactant mixtures.

Caillé analysis of the small-angle X-ray line shape of the lamellar phase of 7:3 wt/wt cetyltrimethylammonium tosylate (CTAT)/sodium dodecylbenzene sulfonate (SDBS) bilayers shows that the bending elastic constant is kappa = (0.62 +/- 0.09)k(B)T. From this and previous results, the Gaussian curvature constant is kappa = (-0.9 +/- 0.2)k(B)T. For 13:7 wt/wt CTAT/SDBS bilayers, the measured bending elasticity decreases with increasing water dilution, in good agreement with predictions based on renormalization theory, giving kappa(o) = 0.28k(B)T. These results show that surfactant mixing is sufficient to make kappa approximately k(B)T, which promotes strong, Helfrich-type repulsion between bilayers that can dominate the van der Waals attraction. These are necessary conditions for spontaneous vesicles to be equilibrium structures. The measurements of the bending elasticity are confirmed by the transition of the lamellar phase of CTAT/SDBS from a turbid, viscoelastic gel to a translucent fluid as the water fraction is decreased below 40 wt %. Freeze-fracture electron microscopy shows that the gel is characterized by spherulite defects made possible by spontaneous bilayer curvature and low bending elasticity. This lamellar gel phase is common to a number of catanionic surfactant mixtures, suggesting that low bending elasticity and spontaneous curvature are typical of these mixtures that form spontaneous vesicles.

Anions↗

PubMed2006

Zero spontaneous curvature and its effects on lamellar phase morphology and vesicle size distributions.

Equimolar mixtures of dodecyltrimethylammonium chloride (DTAC) and sodium octyl sulfonate (SOSo) show a vesicle phase at >99 wt % water and a single, fluid lamellar phase for water fractions below 80 wt %. This combination is consistent with the bilayer bending elasticity kappa approximately k(B)T and zero bilayer spontaneous curvature. Caillé line shape analysis of the small-angle X-ray scattering from the lamellar phase shows that the effective kappa depends on the lamellar d spacing consistent with a logarithmic renormalization of kappa, with kappa(o) = (0.8 +/- 0.1)k(B)T. The vesicle size distribution determined by cryogenic transmission electron microscopy is well fit by models with zero spontaneous curvature to give (kappa + (kappa/2)) = (1.7 +/- 0.1)k(B)T, resulting in kappa = (1.8 +/- 0.2)k(B)T. The positive value of kappa and the lack of spontaneous curvature act to eliminate the spherulite defects found in the lamellar gel phases found in other catanionic mixtures. Current theories of spontaneous bilayer curvature require an excess of one or more components on opposite sides of the bilayer; the absence of such an excess at equimolar surfactant ratios explains the zero spontaneous curvature.

Journal Article↗

PubMed2006

Flexible bilayers with spontaneous curvature lead to lamellar gels and spontaneous vesicles.

Mixtures of cetyltrimethylammonium tosylate (CTAT) and sodium dodecylbenzene sulfonate (SDBS) in water form a fluid lamellar phase at < or = 40 wt % water but surprisingly turn into viscous gels at higher water fractions. The gels are characterized by spherulite and other bilayer defects consistent with a low bending elasticity, kappa approximately k(B)T, and a nonzero spontaneous curvature. Caillé analysis of the small-angle x-ray line shape confirms that for 7:3 wt:wt CTAT:SDBS bilayers at 50% water, kappa = 0.62 +/- 0.09 k(B)T and kappa = -0.9 +/- 0.2 k(B)T. For 13:7 wt:wt CTAT:SDBS bilayers, the measured bending elasticity decreases with increasing water dilution in good agreement with predictions based on renormalization theory, giving kappa(o) = 0.28 k(B)T. These results show that surfactant mixing is sufficient to make kappa approximately k(B)T, which promotes strong, Helfrich-type repulsion between bilayers that can dominate the van der Waals attraction. These are necessary conditions for spontaneous vesicles formed at even higher water fractions to be equilibrium structures.

Journal Article↗

PubMed2005

Inhibition of pulmonary surfactant adsorption by serum and the mechanisms of reversal by hydrophilic polymers: theory.

A theory based on the Smolukowski analysis of colloid stability shows that the presence of charged, surface-active serum proteins at the alveolar air-liquid interface can severely reduce or eliminate the adsorption of lung surfactant from the subphase to the interface, consistent with the observations reported in the companion article (pages 1769-1779). Adding nonadsorbing, hydrophilic polymers to the subphase provides a depletion attraction between the surfactant aggregates and the interface, which can overcome the steric and electrostatic resistance to adsorption induced by serum. The depletion force increases with polymer concentration as well as with polymer molecular weight. Increasing the surfactant concentration has a much smaller effect than adding polymer, as is observed. Natural hydrophilic polymers, like the SP-A present in native surfactant, or hyaluronan, normally present in the alveolar fluids, can enhance adsorption in the presence of serum to eliminate inactivation.

Adsorption↗

PubMed2005

Inactivation of pulmonary surfactant due to serum-inhibited adsorption and reversal by hydrophilic polymers: experimental.

The rate of change of surface pressure, pi, in a Langmuir trough following the deposition of surfactant suspensions on subphases containing serum, with or without polymers, is used to model a likely cause of surfactant inactivation in vivo: inhibition of surfactant adsorption due to competitive adsorption of surface active serum proteins. Aqueous suspensions of native porcine surfactant, organic extracts of native surfactant, and the clinical surfactants Curosurf, Infasurf, and Survanta spread on buffered subphases increase the surface pressure, pi, to approximately 40 mN/m within 2 min. The variation with concentration, temperature, and mode of spreading confirmed Brewster angle microscopy observations that subphase to surface adsorption of surfactant is the dominant form of surfactant transport to the interface. However (with the exception of native porcine surfactant), similar rapid increases in pi did not occur when surfactants were applied to subphases containing serum. Components of serum are surface active and adsorb reversibly to the interface increasing pi up to a concentration-dependent saturation value, pi(max). When surfactants were applied to subphases containing serum, the increase in pi was significantly slowed or eliminated. Therefore, serum at the interface presents a barrier to surfactant adsorption. Addition of either hyaluronan (normally found in alveolar fluid) or polyethylene glycol to subphases containing serum reversed inhibition by restoring the rate of surfactant adsorption to that of the clean interface, thereby allowing surfactant to overcome the serum-induced barrier to adsorption.

Adsorption↗

PubMed2005

Surface ordering of a perfluorinated, self-assembled, dendrimer on a water subphase.

We have investigated the surface ordering of a synthetic, asymmetric, fan-shaped dendrimer containing a carboxyl core and perfluorinated tails which was obtained by the esterification of the intermediary. X-ray diffraction patterns and transmission electron microscopy (TEM) images show the molecules self-assemble into a hexagonal, cylindrical mesophase. Surface pressure-area isotherms and Brewster angle microscopy measurements show the molecule forms a stable monolayer at the air-water interface with a single phase transition. As a condensed monolayer, the perfluorinated tails are well-packed with hexagonal symmetry with (10) spacing of approximately 0.5 nm from molecular-scale atomic force microscopy (AFM) images. Such dense molecular-scale packing has not been observed in other dendritic molecules thus far. Compared to the case of conventional dendritic molecules with alkyl tails, these molecules occupy a much smaller molecular area due to the strong microphase separation between the carboxylic core and perfluorinated tails at the air-water interface. After monolayer collapse, the irregular islands with terrace morphology are observed in contrast with conventional alkyl-terminated self-assembled dendritic molecules where irregular islands do not appear. The interfacial and internal structure of every terrace shows planar columnar morphology from AFM and TEM imaging. From these results, we discuss the stability of perfluorinated, self-assembled dendrimers on water, as well as how to generate planar morphology on a hydrophilic surface.

Journal Article↗

PubMed2005

Keeping lung surfactant where it belongs: protein regulation of two-dimensional viscosity.

Lung surfactant causes the surface tension, gamma, in the alveoli to drop to nearly zero on exhalation; in the upper airways gamma is approximately 30 mN/m and constant. Hence, a surface tension gradient exists between alveoli and airways that should lead to surfactant flow out of the alveoli and elimination of the surface tension gradient. However, the lung surfactant specific protein SP-C enhances the resistance to surfactant flow by regulating the ratio of solid to fluid phase in the monolayer, leading to a jamming transition at which the monolayer transforms from fluidlike to solidlike. The accompanying three orders of magnitude increase in surface viscosity helps minimize surfactant flow to the airways and likely stabilizes the alveoli against collapse.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2005

Modifying calf lung surfactant by hexadecanol.

Monolayer properties such as phase behavior, collapse pressure, and surface viscosity are determined by monolayer composition. Learning how to control these properties through simple additives is important to understanding lung surfactant monolayers and to designing optimal replacement surfactants for treatment of disease. The properties of Infasurf, a replacement lung surfactant derived from calf lung lavage organic extract, can be modified in a controlled fashion by adding hexadecanol (HD). Grazing incidence X-ray diffraction shows that the HD preferentially interacts with dipalmitoylphosphatidylcholine (DPPC), the main phospholipid component of Infasurf, in the same way as in binary mixtures of DPPC and HD. HD intercalates between the DPPC chains, which leads to a tighter packing of the two-dimensional lattice and greater stability of the solid phase. This molecular reorganization triggers changes at the macroscopic scale, leading to a greatly increased solid-phase fraction at a given surface pressure and order of magnitude increases in the surface shear viscosity. However, the collapse pressure decreases, and, hence, the minimum surface tension of the film increases.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2004

More than a monolayer: relating lung surfactant structure and mechanics to composition.

Survanta, a clinically used bovine lung surfactant extract, in contact with surfactant in the subphase, shows a coexistence of discrete monolayer islands of solid phase coexisting with continuous multilayer "reservoirs" of fluid phase adjacent to the air-water interface. Exchange between the monolayer, the multilayer reservoir, and the subphase determines surfactant mechanical properties such as the monolayer collapse pressure and surface viscosity by regulating solid-fluid coexistence. Grazing incidence x-ray diffraction shows that the solid phase domains consist of two-dimensional crystals similar to those formed by mixtures of dipalmitoylphosphatidylcholine and palmitic acid. The condensed domains grow as the surface pressure is increased until they coalesce, trapping protrusions of liquid matrix. At approximately 40 mN/m, a plateau exists in the isotherm at which the solid phase fraction increases from approximately 60 to 90%, at which the surface viscosity diverges. The viscosity is driven by the percolation of the solid phase domains, which depends on the solid phase area fraction of the monolayer. The high viscosity may lead to high monolayer collapse pressures, help prevent atelectasis, and minimize the flow of lung surfactant out of the alveoli due to surface tension gradients.

Biological Products↗

PubMed2004

Synergistic interactions of lipids and myelin basic protein.

This report describes force measurements and atomic force microscope imaging of lipid-protein interactions that determine the structure of a model membrane system that closely mimics the myelin sheath. Our results suggest that noncovalent, mainly electrostatic and hydrophobic, interactions are responsible for the multilamellar structure and stability of myelin. We find that myelin basic protein acts as a lipid coupler between two apposed bilayers and as a lipid "hole-filler," effectively preventing defect holes from developing. From our protein-mediated-adhesion and force-distance measurements, we develop a simple quantitative model that gives a reasonably accurate picture of the molecular mechanism and adhesion of bilayer-bridging proteins by means of noncovalent interactions. The results and model indicate that optimum myelin adhesion and stability depend on the difference between, rather than the product of, the opposite charges on the lipid bilayers and myelin basic protein, as well as on the repulsive forces associated with membrane fluidity, and that small changes in any of these parameters away from the synergistically optimum values can lead to large changes in the adhesion or even its total elimination. Our results also show that the often-asked question of which membrane species, the lipids or the proteins, are the "important ones" may be misplaced. Both components work synergistically to provide the adhesion and overall structure. A better appreciation of the mechanism of this synergy may allow for a better understanding of stacked and especially myelin membrane structures and may lead to better treatments for demyelinating diseases such as multiple sclerosis.

Hydrophobic and Hydrophilic Interactions↗

PubMed2004

Linear dependence of surface drag on surface viscosity.

Flow at an air-water interface is limited by drag from both the two-dimensional surface and three-dimensional subphase. Separating these contributions to the interfacial drag is necessary to measure surface viscosity as well as to understand the influence of the interface on flow. In these experiments, a magnetic needle floating on a monolayer-covered air-water interface is put in motion by applying a constant magnetic force, F(m). The needle velocity varies exponentially with time, reaching a terminal velocity F(m)/C, in which C is the drag coefficient. C is shown to be linearly proportional to the monolayer surface viscosity, eta(s), for dipalmitoylphosphatidylcholine monolayers in the condensed phase by comparison to surface viscosity measured by channel viscometry.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2004

Electrostatic barrier to recovery of dipalmitoylphosphatidylglycerol monolayers after collapse.

The reincorporation of lipids into monolayers at the air-water interface after collapse is important to the maintenance of low surface tensions on subsequent expansion and compression cycles. For single component, anionic dipalmitoylphosphatidylglycerol monolayers, the fraction of recovered lipid is proportional to the subphase ionic strength. The collapse mechanism and structure of the collapsed materials appear unchanged with ionic strength. A simple electrostatic barrier model shows that the fractional recovery depends exponentially on the Debye length; this is verified by experiment. This simple model suggests possible catalytic roles for the cationic lung surfactant specific proteins SP-B and SP-C that induce structural changes in the monolayer that may act as charge-neutralizing docking sites for surfactant in the subphase, leading to faster and more efficient recovery.

Computer Simulation↗

PubMed2002

Viscosity of two-dimensional suspensions.

Over a range of conditions, lipid and surfactant monolayers exhibit coexistence of discrete solid domains in a continuous liquid. The surface shear viscosity, mu(s), of such monolayers collapses onto a single curve: mu(s)/mu(so) = [1-(A/A(c))](-1), in which mu(so) is the viscosity of the liquid phase, A is the area fraction of the solid phase measured by fluorescence microscopy, and A(c) is a critical solid phase fraction. This scaling relationship is directly analogous to that of three-dimensional dispersion of spheres in a solvent with long-range repulsive interactions, with area fraction replacing volume fraction.

Lipids↗

PubMedDate not supplied

Comparison of three lipid formulations for synthetic surfactant with a surfactant protein B analog.

Surfactant protein B (SP-B) is an essential component of pulmonary surfactant. Synthetic dimeric SP-B(1-25) (SP-B(1-25)), a peptide based on the N-terminal domain of human SP-B, efficiently mimics the functional properties of SP-B. The authors investigated the optimum lipid composition for SP-B(1-25) by comparing the effects of natural lung lavage lipids (NLL), a synthetic equivalent of NLL (synthetic lavage lipids SLL), and a standard lipid mixture (TL) on the activities of SP-B(1-25). Surfactant preparations were formulated by mixing 2 mol% SP-B(1-25) in NNL, SLL, and TL. Calfactant, a calf lung lavage extract with SP-B and SP-C, was a positive control and lipids without peptide were negative controls. Minimum surface tension measured on a captive bubble surfactometer was similar for the three SP-B(1-25) surfactant preparations and calfactant. The effects on lung function were compared in ventilated, lavaged, surfactant-deficient rats. Oxygenation and lung volumes were consistently higher in rats treated with calfactant and SP-B(1-25) in NLL or SLL than in rats treated with SP-B(1-25) in TL. Fourier transform infrared spectra observed abnormal secondary conformations for SP-B(1-25) in TL as a possible cause for the reduced lung function. Lipid composition plays a crucial role in the in vitro and in vivo functions of SP-B(1-25) in surfactant preparations.

Amino Acid Sequence↗