AN ANALYTICAL MODEL FOR THE PHASE-BEHAVIOR OF CHOLESTERYL ESTERS IN INTRACELLULAR INCLUSIONS

The cholesteryl ester-rich, intracellular inclusions that characterize atherosclerotic plaque are capable of existing in a metastable, relat ively fluid state for long periods of time. We have developed an analy tical model which explains this metastability, and other aspects of th e phase behavior, of physiologically relevant, phospholipid-stabilized dispersions of cholesteryl ester mixtures. The model, based on classi cal nucleation theory, incorporates temperature, time and lipid compos ition as independent variables. Differential scanning calorimetry was used to elucidate the model. The dispersions consisted of cholesteryl palmitate and an ester containing a long-chain, unsaturated or polyuns aturated, fatty acid. When a dispersion of approx. 1-mu m droplets is melted, then cooled, crystallization is preceded by the formation of s mall crystalline nuclei (homogeneous nucleation). Nucleation is energe tically unfavorable until (typically) well below the melting point. si gma the tension between the surface of the crystal nucleus and surroun ding fluid, is a measure of the difficulty in forming nuclei. This par ameter was found to increase with the content of unsaturated ester. si gma was found to increase with increasing triacylglycerol content, and to decrease upon addition of free cholesterol.