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"Ligand-Receptor Binding Kinetics and Equilibrium on Cell Membrane Mimics"

Jessica Tucker (Advisors: Todd Przybycien and Bob Tilton)

A key to information flow and recognition in cellular processes is receptor-ligand binding on the cell membrane. Knowing how to make receptor-ligand binding more energetically or kinetically favorable is important for the delivery of drugs that target cell surface receptors. An understanding of the parameters that affect receptor-ligand binding is thus crucial in the arenas of cell-cell recognition and drug design and delivery. Some of these factors may include the presence of the glycocalyx that shrouds the membrane, the two-dimensional membrane fluidity, and the areal concentration of receptor. The presence of glycolipids and glycoproteins in a membrane form the glycocalyx that protrudes from the cell’s surface.

From http://sun.menloschool.org/~cweaver/cells/c/cell_membrane/

 

The glycocalyx likely provides steric hindrance for ligands approaching the cell’s surface and will thus retard binding kinetics and may impact the equilibrium constant for association. All of the above effects may be coupled, but we will first focus on the steric hindrance provided by the glycocalyx and perhaps touch on some of these other effects later.

 

First, we will incorporate real issues and structures such as glycolipids into lipid bilayers formed by vesicle deposition to mimic the cell membrane (See below). This structure, a supported lipid bilayer (SLB), is attractive because the bilayer is attached to a surface and can be analyzed by a suitable analytical technique.

 

The effects of membrane parameters on the kinetics and thermodynamics of receptor-ligand binding can then be investigated systematically using techniques such as QCM, surface plasmon resonance (SPR), and optical reflectometry.