(326b) Award Submission: Microrheological Measurements of the Effects of Cholesterol On the Mechanical Properties of Lung Surfactant Monolayers

Cholesterol plays a significant role in biological interfaces, especially in the organization of membrane rafts in cell membranes and in clinical lung surfactants used to treat neonatal respiratory distress. We are particularly interested in lung surfactant (LS) monolayers, where the role of cholesterol remains unclear.  Different clinical surfactants used for treatment of premature infants have widely different cholesterol contents; one of the main difficulties is that even though a small mole fraction of cholesterol (5-10%) has been reported in extracts of mammalian LS, there is still a question whether cholesterol originates from the LS or from cell debris. We show, using a novel, micron-scale surface rheometer, that small fractions of cholesterol dramatically change the elastic and viscous properties of LS monolayers. As little as 2 mol% cholesterol decreases the viscosity of a LS monolayer by two orders of magnitude, while likely enhances the spreading of LS as the alveolar area changes during respiration. 5 mol% cholesterol induces an elastic response in the monolayer, which may help retain LS in the deep lung by resisting the Marangoni flow caused by the surface tension gradient between the deep lung and bronchi. Using a combination of atomic force microscopy and optical fluorescence microscopy, we show the change in monolayer morphology induced by cholesterol provides important clues to the dynamic processes. We conclude that a cholesterol content of about 4 mol% is a critical concentration around which rheological properties can vary dramatically. Subtle changes in composition around this concentration can enable both a low viscosity to improve spreading during respiration, as well as a high elasticity to minimize Marangoni flow out of the lungs.