Heidi E. Warriner

The physics and physiology of lung surfactants

Langmuir monolayers have provided experimentally accessible models for studies of lung surfactants at the air-alveolus interface since the medical necessity of lung surfactant was demonstrated by the pioneering work of Avery and Clements in the early 1960s. The fundamental goal of these in vitro studies is a molecular level understanding of the relationships between lung surfactant composition, monolayer morphology, and monolayer physical parameters such as minimum surface tension, spreading, viscosity, etc.

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 Lα,g, form the gel phase when water is added to the liquid-like lamellar Lα 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 (∼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 Lα,g regime as it sets in from the fluid lamellar Lα 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 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.

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.

Lamellar biogels comprising fluid membranes with a newly synthesized class of polyethylene glycol-surfactants

A series of four polymer–surfactant macromolecules, each consisting of a double-chain hydrophobic moiety attached onto a monofunctional polyethylene glycol (PEG) polymer chain, were synthesized in order to study their effect upon the fluid lamellar liquid crystalline (Lα) phase of the dimyristoylphosphatidylcholine/pentanol/water system. The main finding of this study is that the addition of these compounds induces a new lamellar gel, called Lα,g. We have determined the phase diagrams as a function of PEG–surfactant concentration, cPEG, and weight fraction water, ΦW. All phase diagrams are qualitatively similar and show the existence of the gel. Unlike more common polymer physical gels, this gel can be induced either by increasing cPEG or by adding water at constant cPEG. In particular, less polymer is required for gelation as water concentration increases. Moreover, the gel phase is attained at concentrations of PEG–surfactant far below that required for classical polymer gels and is stable at temperatur...

The bridging conformations of double-end anchored polymer-surfactants destabilize a hydrogel of lipid membranes

Double-end-anchored poly-ethylene-glycol-surfactants (DEA-PEG-surfactants) induce the gelation of lyotropic lamellar Lα phases stabilized by undulation forces. The physical hydrogel (Lα,g) derives its viscoelasticity from the proliferation of defects at a mesoscopic level. The DEA-PEG-surfactants assume both looping and bridging conformations. The existence of novel bridging conformations is indicated by the coexistence of two lamellar phases and the limited swelling of the Lα and Lα,g phases. Modeling of the polymer decorated membranes demonstrates the existence of bridging and yields a rapidly decreasing density of bridging conformations with increasing interlayer spacing.

Collapse Mechanisms of Lung Surfactant Protein DPPG

Lung surfactant plays a crucial role in respiration [1]. Respiratory distress syndrome (RDS) can be caused by the lack of lung surfactant and can lead to death in premature infants [1, 2]. Artificial lung surfactants are being developed to combat RDS, but a fundamental understanding of monolayer collapse is needed to properly design these artificial mixtures. This paper addresses the issue of monolayer collapse at high surface pressures and subsequent respreading. Monolayer collapse has been extensively studied, yet little is known about mechanisms of collapse and respreading [3-5]