Pulmonary surfactant, also known as lung surfactant, is a detergent-like, lipid-protein mixture synthesized by alveolar type II epithelial cells. Adsorption leads to a thin film at the air-water surface of the lung. The major biophysical function of this lung surfactant film is to reduce the alveolar surface tension to near-zero value. However, the biophysical mechanism by which the film reaches such low surface tension is still unknown. Historically available analytical methods and biophysical tools do not allow us to directly visualize the adsorbed lung surfactant film. We have developed a novel methodology called constrained drop surfactometry (CDS) that allows direct imaging of the adsorbed lung surfactant film under physiologically relevant conditions.

The cover art for the August 18 issue of Biophysical Journal is an artistic rendering that illustrates CDS and the biophysical mechanism of lung surfactant. The foreground of this cover image shows one-half of a lung alveolus on the left and one-half of a droplet on the right. The alveolus drawing, courtesy of Charita Goyal, shows a macrophage, as well as type I and type II epithelial cells. For simplicity, the multilayered lung surfactant film is shown in yellow, with only the dipalmitoylphosphatidylcholine (DPPC) monolayer at the air-water surface shown in detail. The droplet drawing, courtesy of Saksham Tandon, shows a water droplet “constrained” on a pedestal with sharp edges. A lung surfactant film is adsorbed at the air-water surface of the droplet. This surfactant film shows the details of “adsorption-induced squeeze-out,” with the solid-like DPPC molecules (red-headgroup) occupying the air-water surface and the fluid-like non-DPPC molecules (green-headgroup) folding into the aqueous side. In addition, the droplet drawing demonstrates two novel techniques that facilitate direct imaging of the adsorbed lung surfactant film. First, it shows a surfactant vesicle being washed away from the droplet using a subphase-replacement technique. Second, it shows a mica surface submerged in the droplet for in situ Langmuir-Blodgett (LB) transfer under controlled conditions. It should be noted that the alveolus (200–300 µm), the droplet (3–5 mm), and the lipid molecules (~2 nm) were not drawn to scale.

The background of this cover image depicts some of the analytical methods and measuring principles behind our biophysical study. An atomic force microscopy (AFM) probe is shown to scan the adsorbed lung surfactant film. It is worth mentioning that this AFM drawing is only imaginary because the actual scan was not carried out on the droplet surface but on an LB transferred sample. Also shown in the background is the axisymmetric drop shape analysis (ADSA) behind CDS and the famous Young-Laplace equation that is simple but essential for understanding the biophysics of lung surfactant and alveolar stability.

We hope our findings about the biophysical mechanism of lung surfactants can be translated into the clinical practice of treating newborn and adult patients with respiratory complications. For example, there are currently multiple clinical trials investigating the surfactant therapy as a potential treatment for COVID-19-induced acute respiratory distress syndrome (C-ARDS).

For more information about lung surfactant and CDS, please see our website at www2.hawaii.edu/~yzuo.

—  Yi Y. Zuo