Understanding the Biophysical Activity of Dysfunctional Lung Surfactant

Lung surfactant lines the air-water interface of the liquid lining found in the alveolar sacs of the lungs and is crucial to breathing. Its interfacial behavior enables the pulmonary surface tension to approach near zero levels. Lung surfactant dysfunction causes difficulty of breathing, alveolar collapse, and possibly death. Acute respiratory distress syndrome (ARDS) is an example of dysfunctional lung surfactant that affects 150,000 people each year in the U.S. with a mortality of 40%. ARDS results from lung injury, which causes blood serum to enter the alveoli and deactivate the lung surfactant. Albumin, a major blood-serum protein, is being studied for its role in this inhibition process. It is believed that albumin occupies the alveolar air-water interface during ARDS, blocking lung surfactant from functioning properly. Previous laboratory studies have shown that certain hydrophilic polymers reverse this inhibition. The goal is to further understand the mechanisms behind the reversal process.

A Langmuir trough acts as an in vitro model lung by mimicking the liquid layer found in the alveoli as well as the expansion and contraction of the lungs during respiration. Fluorescently dyed lung surfactant, albumin, and polymer are imaged using a confocal microscope. Confocal microscopy allows us to simultaneously visualize three components and to optically section the sample. By viewing thin image slices of the sample at various depths, three dimensional measurements of the locations and relative concentrations of lung surfactant, albumin, and polymer can be made. We have modeled and imaged three distinct scenarios: the healthy lung, lung surfactant inhibition, and inhibition reversal. We hope that three dimensional analyses of the interactions between lung surfactant, albumin, and polymer will give insight into how lung surfactant replaces albumin at the air-water interface during the inhibition reversal process.