Overcoming rapid inactivation of lung surfactant: Analogies between competitive adsorption and colloid stability

Abstract

Lung surfactant (LS) is a mixture of lipids and proteins that line the alveolar air-liquid interface, lowering the interfacial tension to levels that make breathing possible. In acute respiratory distress syndrome (ARDS), inactivation of LS is believed to play an important role in the development and severity of the disease. This review examines the competitive adsorption of LS and surface-active contaminants, such as serum proteins, present in the alveolar fluids of ARDS patients, and how this competitive adsorption can cause normal amounts of otherwise normal LS to be ineffective in lowering the interfacial tension. LS and serum proteins compete for the air-water interface when both are present in solution either in the alveolar fluids or in a Langmuir trough. Equilibrium favors LS as it has the lower equilibrium surface pressure, but the smaller proteins are kinetically favored over multi-micron LS bilayer aggregates by faster diffusion. If albumin reaches the interface, it creates an energy barrier to subsequent LS adsorption that slows or prevents the adsorption of the necessary amounts of LS required to lower surface tension. This process can be understood in terms of classic colloid stability theory in which an energy barrier to diffusion stabilizes colloidal suspensions against aggregation. This analogy provides qualitative and quantitative predictions regarding the origin of surfactant inactivation. An important corollary is that any additive that promotes colloid coagulation, such as increased electrolyte concentration, multivalent ions, hydrophilic non-adsorbing polymers such as PEG, dextran, etc. or polyelectrolytes such as chitosan, added to LS, also promotes LS adsorption in the presence of serum proteins and helps reverse surfactant inactivation. The theory provides quantitative tools to determine the optimal concentration of these additives and suggests that multiple additives may have a synergistic effect. A variety of physical and chemical techniques including isotherms, fluorescence microscopy, electron microscopy and X-ray diffraction show that LS adsorption is enhanced by this mechanism without substantially altering the structure or properties of the LS monolayer.

Effect of cholesterol nanodomains on monolayer morphology and dynamics

“…This surface viscosity effect suggests a role for cholesterol in lung surfactant (LS), a lipid-protein monolayer necessary to reduce the surface tension in the lung alveoli during respiration ( Fig. S1) (3,4). At present, even the existence of cholesterol in native LS is questioned, because the lung lavage required to harvest LS inevitably causes blood and cell debris to be coextracted, potentially contaminating LS with cholesterol (5).…”

μ-PIV for the Analysis of Flow Fields near a Propagating Air-Liquid Interface

“…This inactivation is caused by the presence of LS inhibitors, including a variety of water-soluble and surface-active serum protein substances, such as albumin, fibrinogen, and IgG that are normally absent from the airway. These can leak through the capillary membrane from the damaged cells, causing LS to lose its ability to lower surface tension necessary for the lung function (Zasadzinski et al 2010). Mechanical ventilation is inarguably a necessary life-sustaining form of medical intervention at this stage.…”

“…Since inactivated or insufficient amount of lung surfactants are one of important factors for controlling the cellar damage during the airway reopening, diffusive molecular transport of LS near the air-liquid interface including mechanism of competitive adsorption between lung surfactant and the inhibitors are well-studied areas (Refer to the review article of the surfactant inactivation by Zasadzinski et al (2010) for detail.). It is predicted that for the airway reopening case, collapsing and re-spreading process of LS layer at the surface of the progressing semi-infinite bubble tip is dominated by convective transport driven by hydrodynamics movement of the liquid phase (Fig.…”

Closing the gap: accelerating the translational process in nanomedicine by proposing standardized characterization techniques

“…99 In another set of studies, surface roughness and porosity were modulated via variations in the voltage used in synthesis. 91 The different surface topographies demonstrated different protein adsorption initially, but this was not found to have a profound effect on the biological fate of the nanoparticle. 100,101 On the contrary, it was found that changes in the nanocarrier's shape (ie, sphere versus rod) have a pronounced effect on the fate of the nanocarrier.…”

“…88 Varying the pH or increasing the electrolyte concentration generally promotes coagulation of protein colloids, causing them to coalesce more favorably. 91,92 These parameters must be taken into consideration when studying protein-nanoparticle interactions.…”