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Dream : Faculty : Biomaterials : Steven Wrenn
Steven Wrenn
Assistant Professor of Chemical Engineering
Whitaker Award 2001
Pfizer Young Faculty 2002 & 2003
Enzyme-Induced Aggregation of Lipoproteins and Vesicles
Dr. Wrenn’s research deals with biological colloids that transport cholesterol, namely plasma lipoproteins and biliary vesicles, and the mechanism by which cholesterol crystals nucleate from such colloids. Regardless of the level of cholesterol supersaturation, colloidal aggregation appears to be a prerequisite for nucleation, and enzymes that accelerate aggregation also facilitate nucleation. The result is that certain enzymes in bile promote gallstone formation, and similar enzymes in blood exacerbate atherosclerosis. There is strong evidence to suggest that extracelluar enzymes, sphingomyelinase and phospholipase A2, induce aggregation via chemical modification of surface phospholipids on the low-density lipoproteins (LDL) outer monolayer (Fig. 8). Specifically, the cleavage of polar choline head groups, and the exposure of non-polar moieties of ceramide, which ensue, provides a driving force for aggregation as particles attempt to eliminate exposure of hydrophobic regions on the outer monolayer.
Example REU Project: A typical project will involve systematic dynamic light scattering and turbidity studies to quantify colloidal aggregation as a function of enzyme concentration and cholesterol loading. Students will gain a general understanding of light scattering principles and will compare measured particle sizes with those predicted by mass action models. Advanced students will begin to decouple enzyme kinetics from aggregation dynamics and will go on to perform fluorescence experiments that reveal changes in membrane polarity and hydrophobicity; this will provide further insight into the factors which cause the particles to aggregate.
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