Discrepancy between phase behavior of lung surfactant phospholipids and the classical model of surfactant function

The studies reported here used fluorescence microscopy and Brewster angle m icroscopy to test the classical model of how pulmonary surfactant forms fil ms that are metastable at high surface pressures in the lungs. The model pr edicts that the functional film is liquid-condensed (LC) and greatly enrich ed in dipalmitoyl phosphatidylcholine (DPPC). Both microscopic methods show that, in monolayers containing the complete set of phospholipids from calf surfactant, an expanded phase persists in coexistence with condensed domai ns at surface pressures approaching 70 mN/m. Constituents collapsed from th e interface above 45 mN/m, but the relative area of the two phases changed little, and the LC phase never occupied more than 30% of the interface. Cal culations based on these findings and on isotherms obtained on the continuo us interface of a captive bubble estimated that collapse of other constitue nts increased the mol fraction of DPPC to no higher than 0.37. We conclude that monolayers containing the complete set of phospholipids achieve high s urface pressures without forming a homogeneous LC film and with a mixed com position that falls far short of the nearly pure DPPC predicted previously. These findings contradict the classical model.