(319i) Inactivation of Lung Surfactant By Phospholipase-Catalyzed Degradation

The alveoli of human lungs are lined with a thin liquid film and a monolayer of lung surfactant (LS) at the air interface. LS reduces surface tension and stabilizes the lung against collapse and overdistension, and is thus necessary for respiration. Pulmonary diseases such as acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, inactivate LS [1]. However, the inactivation mechanism remains unknown. The lungs of ARDS patients contain increased levels of a phospholipid-hydrolyzing enzyme (PLA₂) that hydrolyzes lipids like DPPC into palmitic acid (PA) and lyso-PC (LPC) [2, 3]. Since PA co-crystallizes with DPPC to form rigid, elastic domains [4], we hypothesize that PLA₂-catalyzed degradation establishes a stiff, heterogeneous rheology in the monolayer, which will impair LS function. Here we study the evolution of a DPPC monolayer as it is degraded by PLA₂. Using interfacial microbutton microrheometry coupled with fluorescence microscopy, we track the stiffness and morphology of the actively degrading monolayer. These results are compared to the stiffness and morphology of mixtures of DPPC and its degradation products, simulating the evolving monolayer composition.

References: [1] Notter, R., "Lung Surfactants: Basic Science and Clinical Applications,'' CRC Press, Boca Raton, FL (2000). [2] Thompson, B. T., et al., "Acute Respiratory Distress Syndrome," N. Engl. J. Med., 377 (6) pp. 562–572 (2017). [3] Nakos, G., et al., "Bronchoalveolar Lavage Fluid Characteristics of Early Intermediate and Late Phases of ARDS," Intensive Care Med. 24 (4) pp. 296–303 (1998). [4] Ding, J., et al., "Viscosity of Two-dimensional Suspensions," Phys. Rev. Lett. 88 (16) pp. 1–4 (2002).