Phospholipids are surface active agents and comprise the major component of cell membranes and of lung surfactant. Here, we are especially interested in lung surfactant (LS), which is found at the air-fluid interface of lung alveoli and lowers the surface tension of lungs so that respiration is possible. In particular, it has been hypothesized that dynamic response properties of surfactant monolayers, such as the viscosity and elasticity, are important for their stability, function, and dynamics. For example, extremely low surface tension in alveoli maintained by lung surfactant monolayers establishes a strong driving force that would tend to drive the LS out of the lung into the upper air ways. High viscosity has been proposed to retard the dynamics of expulsion, and thus it keep in the lung.

In this dissertation, we examine the dynamic response properties (e.g. viscosity, elasticity, yield stress) of phospholipid monolayers at the air-water interface, and relate them to deformation dynamics of the surfactant micro-structure. We use interfacial microrheology, fluorescence microscopy, and atomic force microscopy (AFM) to investigate the dependence of these properties and microstructure on surface pressure, the presence of cholesterol, and the enantiomeric excess. For example, the high surface viscosity at high surface pressure of DPPC film and the relatively high elasticity of DPPC:cholesterol film would resist the surface tension gradient-driven flow of lung surfactant out of the alveoli during exhalation. However, during inhalation, a low viscosity is necessary for the LS to quickly spread to cover the area of the alveolar interface. This dissertation reveals important relationships between dynamics of model lung surfactant monolayers as they deform, and the molecular and micro-structure of the monolayers themselves. This work provides a important step for resolving the role of phospholipid and cholesterol in human lung surfactant and in guiding design of replacement surfactants for clinical use.