Polymer attaching to a surface

Polymer attaching to a surface A polymer binds to a surface in a computer simulation. The blue sites on the surface stick loosely to the yellow subunits of the polymer. The polymer can bind very tightly because of the combined attraction between multiple polymer sites and the surface. Notice that binding is not a discrete process: various parts of the polymer attach and detach before forming a tight bond. The time series goes from right to left, top to bottom. The inset, a top view of the last frame, shows that the polymer has clustered the blue sites on the surface.

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Paper

 Boas, Franz Edward. (1999) "Polyvalent Inhibitors of Pseudomonas aeruginosa Adhesion." Senior honors thesis, Harvard University.

Thesis advisor: Prof. George Whitesides, Dept of Chemistry and Chemical Biology, Harvard.
Supervisor: Dr. Michael Liang
Special thanks to: Prof. Gerald Pier, Dr. Tanweer Zaidi, Prof. Eugene Shakhnovich

Abstract
     We synthesized polymers displaying multiple copies of a peptide from the cystic fibrosis transmembrane conductance regulator (residues 108-117).  This peptide is the minimal sequence needed for binding of Pseudomonas aeruginosa.  Using an in vitro bacterial internalization assay, our preliminary results indicate that such a polyvalent ligand can prevent P. aeruginosa from attaching to (and being internalized by) epithelial cells.  The most effective polymer we synthesized was a polyacrylamide with CFTR peptide covalently attached to 0.5% of its acrylamide subunits.  This polymer has an IC50 value of 700 pM, 40,000 times lower than monovalent CFTR peptide.  Polyacrylamide at the same concentration does not inhibit internalization.
     We also developed a simulation to qualitatively describe how a polyvalent ligand binds to a surface.  This simulation demonstrates that the polymer binds to the surface cooperatively.  Binding can be enhanced by a larger degree of polymerization, a larger fraction of polymer subunits that can attach to the surface, and greater diffusibility of binding sites on the surface.

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