CAREER: A Systematic Study of Cholesterol (Nano)Domains in Model Lipid Membranes

Drexel University, Philadelphia PA

Investigators

Abstract

Wrenn, Steven P. - Drexel University "CAREER: A Systematic Study of Cholesterol (Nano) Domains in Model Lipid Membranes" This project is a systematic study of cholesterol domain formation that is undertaken to identify the regions in temperature-composition space in which structured domains form. The project would also identify the sensitivity of domain formation to physical parameters such as vesicle curvature and bilayer fluidity and to chemical parameters such as phospholipid chain length, degree of saturation, as well as the head group size and charge, and the kinetics and mechanisms of domain growth. The study of cholesterol domain formation in well controlled, model lipid membrane systems lays a foundation for understanding how cholesterol domains contribute to cholesterol nucleation from biological colloids. The research aims to provide a rigorous characterization of the recently discovered cholesterol domains. Specifically, this project consists of an exhaustive phase behavior study to identify regions in temperature-composition space in which cholesterol domains form. These complementary studies provide measurements of domain sizes using a combination of Forster resonance energy transfer and atomic force microscopy. Additional research assess whether domain size is sensitive to membrane curvature. Mathematical models and simulations are included to validate or refute experimental findings. Broader Impacts Cholesterol crystals in the body can be deadly. There are few fundamental studies describing how cholesterol crystallizes from colloidal particles such as vesicles or lipoproteins. The formation of cholesterol crystal may be the reason for a heart attack due to the sudden rupture of an atherosclerosic plaque. Cholesterol crystals may also explain the formation of gallstones. In both cases, the results from this research may prove to be useful in preventing cholesterol crystallization in the body. In terms of social and educational impact, a new mentorship program will target inner city students from Philadelphia, taking advantage of Drexel's close proximity, and will be called Philadelphia Inner City Education via Mentorship for the Under-Privileged (PIC-EM-UP). In particular, a dozen students will be selected from Philadelphia high schools and will be grouped into four teams of three students each. Each team will work alongside a faculty mentor on a mini-project relating to the faculty mentor's research area for one week. The research on cholesterol domains proposed herein will constitute one of the projects entitled "Cholesterol: The Good, the Bad, and the Nuclei." Each week, the teams will switch faculty mentors, working with a total of four mentors and four projects over a four-week period. A high school teacher will participate as a chaperone and will circulate among all teams to help students feel more comfortable in their new research environment.