Modulation of lipid domain formation in mixed model systems by proteins and peptides

UNCW Author/Contributor (non-UNCW co-authors, if there are any, appear on document)
Alexis Jean Oldham (Creator)
The University of North Carolina Wilmington (UNCW )
Web Site:
Sridhar Varadarajan

Abstract: The control of lipid domain formation in biological membranes has received limited consideration. This mechanism is quantitatively investigated using Monte Carlo computer simulations of a simple model system. Monte Carlo simulations are performed on a simple model system composed of phosphatidylecholine (PC), phosphatidylserine (PS), and cholesterol (Chol). Domain formation induced by binding of the phospholipid binding proteins, annexin A5 (A5) and the C2 protein motif is investigated. Simulations for models containing PC/PS lipids indicate that the addition of A5 does not induce lipid domain formation while binding of C2 greatly induces lipid domain formation. The addition of Chol to PC/PS systems was found to induce lipid demixing in the absence and presence of A5 and further enhance the ability of C2 to form PS domains. Incorporation of a preferential protein-protein interaction to PC/PS and PC/PS/Chol systems was found to further increase lipid demixing for all compositions. Lipid domain formation is also investigated experimentally using fluorescence resonance energy transfer (FRET) in 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/ sphingomyelin from porcine brain (BSM)/ Cholesterol (Chol) model systems. Studies have shown that these model systems contain lipid domains. The dependence of lipid domain size upon the addition of the transmembrane region of the linker for activation of T-cells (LAT), a protein believed to associate with lipid rafts, is investigated. When incorporated, LAT was found to insert into both the liquid-ordered (Lo) and liquid-disordered (Ld) regions indicating no lipid specificity. FRET between an acceptor/donor pair shown to not be affected by addition of LAT in POPC/BSM/Chol mixtures indicating that the presence of LAT does not affect the size of lipid domains.

Additional Information

A Thesis Submitted to the University of North Carolina at Wilmington in Partial Fulfillment of the Requirement for the Degree of Masters of Science
Language: English
Date: 2009
Lipid membranes--Analysis, Lipid membranes--Mathematical models, Membrane lipids, Monte Carlo method, Protein binding, Bilayer lipid membranes--Analysis, Lipids, Membrane lipids
Monte Carlo method
Lipid membranes -- Mathematical models
Bilayer lipid membranes -- Analysis
Lipid membranes -- Analysis
Protein binding
Membrane lipids
Membrane lipids

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