The primary objectives of this proposal are to determine energetic and structural factors responsible for the stability of binary and ternary micelles formed between bile salts, lecithin and cholesterol. Two specific questions will be attacked. First, are there structural subdomains within lecithin--bile salt micellar aggregates whose stability and occurence change the properties of the micelles, particularly with respect to solubilizing ability of the micelles for cholesterol? Question two relates to what are the properties and compositions of paracrystalline phases which form at the solubility boundaries for cholesterol in the lecithin-bile salt mixed micelles. Using the techniques of differential scanning calorimetry and fluorescence probe measurements, it is hoped that new information can be obtained which will shed light on the complex behavior of cholesterol in the lecithin-bile salt mixed micelles. Since these aggregates are responsible for the movement of cholesterol through the biliary tract, the results of these investigations could provide a framework for understanding cholesterol gallstone formation. A suitable model of cholesterol precipitation behavior could yield new ideas on the pathogenesis of gallstone disease.
