(502b) Dynamic Regulation of Bioactive Ligands Presented On Gold Particles

We have developed a platform to dynamically regulate the presentation of bioactive ligands immobilized on gold particles to cell surface receptors. The cell-adhesive peptide Arg-Gly-Asp (RGD) was chosen as a model ligand. A polypeptide cysA-RGD, in which A was a leucine zipper domain and cys was a cysteine residue, was synthesized. Gold particles were functionalized with cysA-RGD through the thiol-gold reaction, and the functionalized gold particles were immobilized on N-hydroxysuccinimide(NHS)-functionalized substrates through the amine-NHS reaction. Presentation of RGD to cell surface receptors, as indicated by cell adhesion, could be reversibly regulated by co-immobilization and removal of B-PEG conjugate, in which PEG was polyethylene glycol and B was another leucine zipper that could heterodimerize with A. Cells adhered on these substrates were detached upon addition of B-PEG, which was co-immobilized through A/B heterodimerization and shielded RGD from access to cell surface receptors. The shielded RGD could be converted back to cell-accessible state by the addition of soluble A, which competed with the immobilized A for binding to B and removed B-PEG from the substrates. The platform can be readily adapted to dynamically regulate the presentation of other bioactive ligands of interest.