The purpose of this project is to make block copolymer vesicles that reproduce the ability of leukocytes to interact and bind to endothelium. Leukocytes have the ability to traffic in the blood stream, yet bind firmly to cells in the area of inflammation or infection. By transplanting the molecules that govern these interactions onto the surface of a polymer vesicle, we hypothesize that the resulting polymer vesicles will interact and bind to model endothelium surfaces.
The first aim i s to create a polymer vesicle that will roll, or undergo a unique type of dynamic friction that is characteristic of selectin binding between neutrophils and endothelium.
The second aim i s to create a polymer vesicle that will both roll and firmly bind by modifying the surface to express receptors for both selectin and integrin binding. The ligands for selectin and integrin binding will be attached to the polymer vesicles by modifying the hydrophilic block of the polymer, poly(ethylene glycol), to react with either a primary amine terminated ligand, or through a hierarchical strategy that takes advantage of biotin-avidin binding and the availability of biotinylated ligands.
The third aim of this project is to modulate the binding of leukocyte mimics through the manipulation of the polymer vesicle membrane. The degree of crosslinking and chemistry of the polymer membrane may be varied to reproduce or exceed the structure and strength typical of cell membranes.
| Lin, John J; Bates, Frank S; Hammer, Daniel A et al. (2005) Adhesion of polymer vesicles. Phys Rev Lett 95:026101 |
| Lin, John J; Silas, James A; Bermudez, Harry et al. (2004) The effect of polymer chain length and surface density on the adhesiveness of functionalized polymersomes. Langmuir 20:5493-500 |
