Phase transitions of the pulmonary surfactant film at the perfluorocarbon-water interface

Pulmonary surfactant is a lipid-protein complex that forms a thin film at the air-water surface of the lungs. This surfactant film defines the elastic recoil and respiratory mechanics of the lungs. One generally accepted rationale of using oxygenated perfluorocarbon (PFC) as a respiratory medium in liquid ventilation is to take advantage of its low surface tensions (14-18 mN/m), which was believed to make PFC an ideal replacement of the exogenous surfactant. Compared with the exten-sive studies of the phospholipid phase behavior of the pulmonary surfactant film at the air-water surface, its phase behavior at the PFC-water interface is essentially unknown. Here, we reported the first detailed biophysical study of phospholipid phase transitions in two animal-derived natural pulmonary surfactant films, Infasurf and Survanta, at the PFC-water interface using constrained drop surfactometry. Constrained drop surfactometry allows in situ Langmuir-Blodgett transfer from the PFC-water interface, thus permitting direct visualization of lipid polymorphism in pulmonary surfactant films using atomic force microscopy. Our data suggested that regardless of its low surface tension, the PFC cannot be used as a replacement of pulmonary surfactant in liquid ventilation where the air-water surface of the lungs is replaced with the PFC-water interface that features an intrinsically high interfacial tension. The pulmonary surfactant film at the PFC-water interface undergoes continuous phase transitions at surface pressures less than the equilibrium spreading pressure of 50 mN/m and a monolayer-to-multilayer transition above this critical pressure. These results provided not only novel biophysical insight into the phase behavior of natural pulmonary sur-factant at the oil-water interface but also translational implications into the further development of liquid ventilation and liquid breathing techniques.SIGNIFICANCE Current liquid ventilation and liquid breathing techniques routinely use perfluorocarbon as the respiratory medium, taking advantage of its high oxygen and carbon dioxide solubility and low surface tensions. However, when the lungs are fully or partially filled with the perfluorocarbon, it is the perfluorocarbon-water interfacial tension rather than the perfluorocarbon-air surface tension that determines the interfacial properties of the alveolar surface. Hence, exogenous surfactant has been found to significantly improve the pathological outcome of liquid ventilation. Here, we report the first detailed biophysical study of lipid polymorphism in natural pulmonary surfactant films at the perfluorocarbon-water interface using constrained drop surfactometry, thus providing novel translational implications into the further development of liquid ventilation and liquid breathing techniques.