Evolution of interfacial mechanics of lung surfactant mimics progression of acute respiratory distress syndrome.

How acute respiratory distress syndrome progresses from underlying disease or trauma is poorly understood, and there are no generally accepted treatments resulting in a 40% mortality rate. However, during the inflammation that accompanies this disease, the phospholipase A2 concentration increases in the alveolar fluids leading to the hydrolysis of bacterial, viral, and lung surfactant phospholipids into soluble lysolipids. We show that if the lysolipid concentration in the subphase reaches or exceeds its critical micelle concentration, the surface tension, γ, of dipalmitoyl phosphatidylcholine (DPPC) or Curosurf monolayers increases and the dilatational modulus, [Formula: see text], decreases to that of a pure lysolipid interface. This is consistent with DPPC being solubilized in lysolipid micelles and being replaced by lysolipid at the interface. These changes lead to [Formula: see text] which is the criterion for the Laplace instability that can lead to mechanical instabilities during lung inflation, potentially causing alveolar collapse. These findings provide a mechanism behind the alveolar collapse and uneven lung inflation during ARDS.

Reply to the 'Comment on "Bilayer aggregate microstructure determines viscoelasticity of lung surfactant suspensions"' by J.-F. Berret, DOI: 10.1039/d2sm00653g.

In their comment, Berret suggests that Curosurf, one of three clinical lung surfactant aqueous suspensions examined in the Soft Matter, 2021, 17, 5170-51820 is a Newtonian liquid rather than a shear-thinning soft solid with a small, but measurable yield stress. We postulate that these discrepancies may be due to the size of the magnetic wire measurement probe used in their paper (Thai et al., Colloids Surf., B, 2019, 178, 337-345) the diameter of which is similar in size to the Curosurf bilayer agregates (1-10 µm). The cone and plate rheometer used by Ciutara and Zasadzinski measures averaged effects over the entire macroscopic sample. Our combined results point out that the local viscoelastic properties of a moderately dense suspension may be different than its bulk properties.

Bilayer aggregate microstructure determines viscoelasticity of lung surfactant suspensions.

Neonatal respiratory distress syndrome (NRDS) is treated by intratracheal delivery of suspensions of animal-derived lung surfactant in saline. Lung surfactants are extracted via organic solvents from animal lung lavage, followed by solvent removal and surfactant re-hydration to form multi-bilayer particles suspended in saline. Following intra-tracheal administration, the surfactant suspension spreads throughout the lungs by surface tension gradient induced flow; the spreading rate is limited by suspension viscoelasticity. Here we examine the rheology of three clinical lung surfactant suspensions: Survanta (bovine lung), Curosurf (porcine lung), and Infasurf (calf lung). These surfactants have widely different rheological properties that depend on the lipid composition and bilayer organization. The steady shear viscosity is related to the bilayer particle volume fraction as for a suspension of hard spheres, but the lipid volume fraction is not simply related to the mass loading. Optical and electron microscopy and small angle X-ray scattering show that the viscosity variation is due to the temperature and composition dependent bilayer aggregate shapes and internal particle organization. Survanta forms crystalline bilayers at 37 °C, resulting in high aspect ratio asymmetric particles. Infasurf forms aggregates of unilamellar vesicles containing water pockets, while Curosurf forms onion-like multi-layered liposomes. While the mass loading of the three clinical surfactants is different, the different bilayer organization causes the particle volume fractions to be similar. Adding polyethylene glycol dehydrates and partially flocculates the bilayer aggregates in all suspensions, leading to smaller particle volume fractions and a reduced suspension viscosity even though the solvent viscosity increases almost six-fold.

New experiments and models to describe soluble surfactant adsorption above and below the critical micelle concentration.

HYPOTHESIS: Lysopalmitoylphosphatidylcholine (LysoPC) is a soluble single-chain surfactant product of the innate immune system degradation of double-chain phospholipids. LysoPC adsorption to the air-water interface in lung alveoli can be modeled using alveolar-sized bubbles of constant surface area in a capillary pressure microtensiometer to show that adsorption is diffusion limited both below and above the critical micelle concentration (CMC). Above the CMC, a local equilibrium model is proposed in which depletion of the local monomer concentration drives dissociation of micelles in a region near the bubble surface. EXPERIMENTAL: A capillary pressure microtensiometer in which a feedback loop maintains a constant bubble radius and surface area is used to measure dynamic surface tension during LysoPC adsorption. Direct numerical solution of the spherical diffusion equations, a new three parameter virial equation of state for interface thermodynamics, and a local equilibrium model of micellization above the CMC are used to accurately model the dynamic surface tension experiments both below and above the LysoPC CMC. FINDINGS: LysoPC adsorption is shown to be diffusion-limited over concentrations ranging from below to well above the CMC, and to be well described by a local equilibrium model at concentrations above the CMC. Modelling the dynamic surface tension provides a reliable estimate of the micelle diffusivity near the CMC that is difficult to obtain by other methods in systems with low CMCs.

Dilatational and shear rheology of soluble and insoluble monolayers with a Langmuir trough.

HYPOTHESIS: The surface dilatational and shear moduli of surfactant and protein interfacial layers can be derived from surface pressures measured with a Wilhelmy plate parallel, ΔΠpar and perpendicular ΔΠperp to the barriers in a Langmuir trough. EXPERIMENTAL: Applying area oscillations, A0+ ΔAeiωt, in a rectangular Langmuir trough induces changes in surface pressure, ΔΠpar and ΔΠperp for monolayers of soluble palmitoyl-lysophosphatidylcholine (LysoPC), insoluble dipalmitoylphosphatidylcholine (DPPC), and the protein ß-lactoglobulin to evaluate Es∗+Gs∗=A0ΔΠparΔA and Es∗-Gs∗=A0ΔΠperpΔA. Gs∗ was independently measured with a double-wall ring apparatus (DWR) and Es∗ by area oscillations of hemispherical bubbles in a capillary pressure microtensiometer (CPM) and the results were compared to the trough measurements. FINDINGS: For LysoPC and DPPC, A0ΔΠparΔA≅A0ΔΠperpΔA meaning Es∗≫Gs∗ and Es∗≅A0ΔΠparΔA≅A0ΔΠperpΔA. Trough values for Es∗ were quantitatively similar to CPM when corrected for interfacial curvature. DWR showed G∗ was 4 orders of magnitude smaller than Es∗ for both LysoPC and DPPC. For ß-lactoglobulin films, A0ΔΠparΔA>A0ΔΠperpΔA and Es∗ and Gs∗ were in qualitative agreement with independent CPM and DWR measurements. For ß-lactoglobulin, both Es∗ and Gs∗ varied with film age and history on the trough, suggesting the evolution of the protein structure.