(580g) Cholesterol Induced Morphological Transitions and Their Effect on Model Lung Surfactant Monolayer Rheology

The first synthetic human lung surfactant replacement, Exosurf, was a mixture of dipalmitoylphosphatidylcholine (DPPC), hexadecanol (HD) and tyoloxopol. HD assists in the crystallization of DPPC at low surface pressures by relieving the tilt frustration caused by the incompatible area requirements of the DPPC headgroup and chains. However, when cholesterol, a likely contaminant of lung surfactant due to its ubiquitous presence in the cells lining the alveolus, is added to the DPPC/HD mixture at low (1-8 mol%) concentrations, a remarkable structural evolution occurs on film compression. The crystalline domains of DPPC/HD take on a asymmetric oblong shape with a well defined cusp at low compression, which then undergoes a fingering instability on further compression. Distinct fingers emerge from the oblong domains on the side opposite the cusp, which, over time elongate into extended high aspect ratio linear domains. This structural transition is accompanied by a significant change in the surface viscosity of the monolayer as measured by a microbutton rheometer. The transition is likely due to the effects of cholesterol on reducing the line tension between the crystal and liquid phases of the monolayer, along with the tilt anisotropy of the DPPC/HD crystal. We have found the structural transition is reversible, and can be visualized with lipid fluorescent dyes in the monolayer or with soluble fluorescent dyes in the subphase. At higher cholesterol fractions, the final high aspect ratio structures are chiral with a distinct handedness which likely is also related to the chiral DPPC/HD crystal packing.