Role of Monolayer Curvature in Lung Surfactant Morphology and Mechanics

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ABSTRACT: Native lung surfactant (LS) coats the air-water interface of the pulmonary alveoli, reducing its sur- face tension and stabilizing the lung from collapse. Virtually every important feature of LS – e.g., surface-tension lowering and respreading ability, fluidity, collapse resistance, and gas permeability – depends on its two-dimen- sional (2D) domain microstructure. Recent evidence suggests that the morphology of LS crystalline domains (5- 30 μm in size) are highly sensitive to the curvature of the alveolar air-water interface (radii of curvature of 40- 150 μm). Traditional macroscopic methods of physicochemical analysis, such as Langmuir-Wilhelmy surface tensiometry or pulsating bubble surfactometry, do not examine LS at these microscopic length scales. This omis- sion leaves the clinical community with, at best, an incomplete picture of how different chemical components of LS interact within their native, highly curved environment. At worst, the microscopic curvature of the alveoli plays a nontrivial role in the pathogenesis of pulmonary diseases such as acute respiratory distress syndrome (ARDS). We hypothesize a mechanism of ARDS progression by which enzyme degradation and blood serum protein adsorption fundamentally alters the mechanical and morphological properties of curved LS monolayers. In our putative mechanism, initial injury to the lung causes inflammation and elevated levels of phospholipase A2 (PLA2) and blood serum proteins (e.g., albumin and fibrinogen) in the alveolar hypophase. PLA2 digests phospholipids to produce fatty acids, which co-crystallize with LS to form stiff domains. Fibrinogen adsorbs and intercalates the 2D fluid phase of LS, forming a domain-templated elastic network and inhibiting re-adsorption of LS. Well estab- lished principles of continuum mechanics suggest that highly elastic monolayers with stiff heterogeneities will locally resist changes in curvature, causing anisotropic dilatation or alveolar collapse during respiration. Such abnormalities would not only result in decreased alveolar recruitment, but promote further inflammation and ultimately higher levels of serum protein and PLA2. Since this mechanism depends inherently on the microscopic curvature of the alveoli, it could not be elucidated through conventional physicochemical assays. To test our hypothesis, I will measure and model the impact of fatty acid, cholesterol, and fibrinogen on LS monolayers formed on spherical microbubbles under physiologically relevant conditions. Cholesterol and fatty acid are present in certain clinical LS replacements, while fatty acid and fibrinogen are implicated in the progres- sion of ARDS. I will use a novel tensiometer to measure the microstructure and surface tension of LS-coated, spherical microbubbles as a function of chemical composition and bubble radius. We expect dramatic differences in the morphology and mechanics of curved LS from those revealed by traditional Langmuir-Wilhelmy measure- ments of planar LS. Finally, our proposal contains a significant modeling component. I will use continuum theory to model the static and dynamic morphologies of curved LS monolayers, which will help connect variations in chemical makeup to the material and geometrical aspects of normal and pathological (i.e., ARDS-afflicted) LS.