Dissertation
The effect of lipid composition on cholesterol-rich domain size in model membranes
Doctor of Philosophy (Ph.D.), Drexel University
May 2008
DOI:
https://doi.org/10.17918/etd-2809
Abstract
Lipid rafts are ordered domains of the cell membrane, enriched in cholesterol, sphingolipids, and saturated phospholipids, which are hypothesized to allow a number of cellular processes to occur. Because raft coalescence or division drives many of these cellular processes, they are dependant not only on the presence of lipid rafts, but also on raft size. This work uses steady-state fluorescent techniques, along with a mathematical model, to detect and estimate the size of lipid domains in membrane systems modeling natural cell membranes. The fluorescence study was initially performed on a simple two-component phospholipid and cholesterol system in order to characterize the behavior of the fluorescent probes using a well-established phase diagram and was then extended to more biologically-relevant, three-component systems. Lipid composition and the resulting line tension were found to be the most significant factors affecting domain size and presence. The kinetics of domain growth and dissipation due to change in composition was determined. The two processes were found to occur on much different timescales, with domain growth occurring within several hours and domain dissipation occurring within several seconds. In addition, the rate of cholesterol removal by [beta]-cyclodextrin was found to be strongly phase-dependent, extracting cholesterol preferentially from the ld phase over the lo phase. The role of lipid rafts in two disease processes, bacterial toxin binding and gallstone formation, was also investigated. A. actinomycetemcomitans produces several virulence factors, one of which, a cytotoxin, was found to bind directly to membranes containing lipid rafts, while the leukotoxin was found not to bind directly to membranes, regardless of the phase. Estrogen was found to disrupt lipid rafts, suggesting that it may act as a pro-nucleating agent in the formation of gallstones.
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Details
- Title
- The effect of lipid composition on cholesterol-rich domain size in model membranes
- Creators
- Angela Carin Brown - DU
- Contributors
- Steven P. Wrenn (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Chemical (and Biological) Engineering (1970-2026); College of Engineering (1970-2026); Drexel University
- Other Identifier
- 2809; 991014632216104721