(490d) Mechanistic Insight into Decrease in Lung Surfactant Modulus As Acute Respiratory Distress Progresses | AIChE

(490d) Mechanistic Insight into Decrease in Lung Surfactant Modulus As Acute Respiratory Distress Progresses


Ciutara, C. - Presenter, University of Minnesota
Zasadzinski, J., University of Minnesota
Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by severe breathing difficulties affecting 200,000 people in the US annually with no known cure and 40% mortality. Mortality attributable to COVID-19 often occurs through the progression of pneumonia-induced ARDS. ARDS begins with trauma to the lung which triggers an inflammatory response that leads to increased permeability of alveolar-capillary barriers. Due to the enhanced permeability, phospholipases, serum proteins, and other components of the innate immune system flood the alveolar spaces. Of particular interest is the creation of soluble single-chain lysolipids from the hydrolysis of insoluble phospholipids leading to lysis of bacterial and viral cell membranes. The resulting increased concentration of surface-active lysolipids in the alveolar fluids leads to alterations in the interfacial properties of native lung surfactants.
We hypothesize that these phenomena lead to mechanical instabilities in lung inflation through a dynamic evolution of the interfacial composition which leads to a significant decrease in the dilatational modulus of the pulmonary surfactant monolayer. This decrease in the dilatational modulus can lead to the Laplace Instability, in which smaller alveoli deflate, and larger alveoli are distended, which are typical symptoms of ARDS. Through interfacial rheology, confocal imaging, and isotherm compression experiments, we systematically show that the mechanism by which the dilatational modulus of lung surfactant monolayer decreases is lysolipid concentration-dependent and follows a pathway analogous to membrane solubilization by the small micellar lysolipids. First, we provide mechanistic insight into the evolution of lung mechanics throughout ARDS progression, which can lead to new therapeutic interventions to treating ARDS; second, our observation is the first of its kind that documents the solubilization of an insoluble monolayer at air/water interface by a physiologically important product of inflammation, adding to the vast array of exciting interfacial phenomena to explore.