(319j) Cholesterol Induced Morphological Instabilities and Transitions in Phospholipid Monolayers

Lung surfactant (LS) is a lipid-protein mixture that forms a monolayer that lines the alveolar air-liquid interface and acts to reduce the interfacial tension to a level necessary for breathing. The lack or inhibition of LS can be life threatening, and can result in acute respiratory distress syndrome (ARDS) which has a 40% mortality rate. Due to the complexity of native LS, 2 or 3 component mixtures are studied to elucidate the relationship between composition, monolayer microstructure, and phase behavior and how these factors affect physiological function. The primary lipid in LS is dipalmitoylphosphatidylcholine (DPPC) which accounts for 40-80 percent of native and replacement LS therapies. The addition of fatty acids, fatty alcohols, and cholesterol to replacement LS therapies is controversial. To address the role of these components on monolayer properties, we focus on mixtures of DPPC and hexadecanol (HD) or palmitic acid (PA) with small mole fractions of dihydrocholesterol (DChol). Of particular interest is the 2-dimensional microstructure of LS films as lipids self-assemble to form crystalline-like domains (liquid-condensed phase) within a liquid-like matrix (liquid-expanded phase). By spreading LS monolayers with trace amounts of fluorescent dye, the microstructure of these films can be observed via confocal microscopy. It is found that HD or PA and DPPC co-crystallize to form semi-circular domains that do not change shape with monolayer compression. With the addition of 1.5 mol% DChol to the DPPC/HD or DPPC/PA system, a finger instability is observed during monolayer compression followed by a time dependent circle-to-stripe transition at a fixed interfacial tension. The resultant stripes are of uniform width and variable length and provide the first quantitative experimental confirmation of McConnell’s theory of shape transitions. Measuring the stripe widths provide the first measurements of the Bond Number (ratio of the square of the dipole density difference to the domain line tension) as a function of composition, interfacial tension, and temperature for systems at liquid condensed – liquid expanded phase coexistence.