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PNAS Plus Significance Statements

Cholesterol is currently removed from most lung surfactant extract preparations used in clinical applications. Cholesteroldepleted samples are also used in most in vitro studies of the lung surfactant layer. In our study we have performed a detailed molecular characterization of the structure of the lung surfactant with regard to cholesterol content and temperature. We show that cholesterol has a strong impact on the phase behavior, structure, and dynamics of the lung surfactant system even at low concentrations. We emphasize the importance of controlling the cholesterol content of the lung surfactant system studied to better mimic the endogenous lung surfactant and develop better preparations for clinical treatments. (See pp. E3592–E3601.)