Engineering the Nanoparticle-Protein Interface
Nanomaterials are finding widespread use in biomedical applications. In particular, the ability of nanoparticles to penetrate into every corner of physiological systems suggests that they have applications in therapeutic strategies or as diagnostic tools. However, the potential benefits are not without risk. Interactions of nanoparticles with biological systems can have unintended or even lethal consequences. Therefore, understanding the interaction between these materials and biological media, from a physiochemical point of view, is important in the development of materials that are effective and safe. Furthermore, the ability to chemically engineer nanomaterials that may recognize, bind, and release particular biomacromolecules is of benefit for a variety of in vitro biotechnology applications. This dissertation aims to elucidate the important physiochemical attributes of N-isopropylacrylamide (NIPAm) based polymeric nanoparticles (NPs) that contribute to the interactions between NIPAm NPs and biomacromolecules such as proteins or peptides.
A substantial collection of literature exists concerning the interactions between biological molecules and synthetic materials. These publications cover both fundamental evaluations of the interaction as well as practical biological applications. The first chapter of this dissertation is a brief review of the current literature concerning the interactions between synthetic materials and proteins and how this information applies to NIPAm NPs. A number of applications using these materials is also highlighted. In the second chapter, NIPAm NPs containing aromatic co-monomers are evaluated as synthetic affinity reagents for biological molecules. The ability of the NPs to bind and sequester a cytolytic peptide released by virulent strains of antibiotic resistant bacteria was evaluated in vitro with a quartz crystal microbalance, and in cell based assays. The aromatic components were shown to be significant contributors to the NP-peptide interaction and modification of the aromatic interaction was used to alter the affinity and capacity of the material to the target peptide. The third chapter provides a detailed study on the effects of monomer hydrophobicity, functional group proximity, and the NPs structure to the NIPAm NP-protein interaction. An important conclusion from this evaluation is that both the monomer distribution and NP structure are significant contributors to the NP-protein interaction, thus in the final chapter, the structure and co-monomer distribution within NIPAm NPs are evaluated using small angle neutron scattering (SANS).