UC Berkeley

Smart biomaterials that can actively respond to and interact with their environment are sought after for regenerative medicine, therapeutic delivery, sensing, and actuation. Polymer-nanoparticle hybrids are a promising class of smart materials, but thus far the choice of polymers has predominantly been chemically synthesized ones. In contrast, natural tissues commonly utilize proteins to interface with nanoparticles and provide smart functionalities. Inspired by nature, this dissertation describes the development of genetically engineered, protein-based polymers (PBPs) for use as components of smart, polymer-nanoparticle hybrids. Specifically, elastin-like polypeptides (ELPs), a class of thermoresponsive PBPs, were utilized to functionalize two nanoparticles.

First, an improved method for synthesizing PBP genes was developed. Crafting new PBPs is limited by the ease with which their genes can be engineered. The new method utilizes a specific architecture of restriction enzymes to address some of the drawbacks of previous methods and was used to efficiently and accurately produce ELP genes.

Next, ELPs were engineered to display biomimetic, bone mineral-binding peptides and their effect on therapeutic bone cements was investigated. Bones are mechanically robust, composites composed predominantly of proteins and nanocrystalline mineral. In contrast, bone cements are brittle and do not contain organic materials. Composites of mineral-binding ELPs and cement had significantly improved strength. Furthermore, the injectability and washout resistance of cements were improved as a result of the ELP's thermoresponsive behavior.

Finally, photoresponsive composites were created by engineering ELPs to display graphene-binding peptides. Graphene-derived nanoparticles (GNs) exhibit unique mechanical, electrical, and optical properties but are difficult to integrate into biological systems due to their hydrophobic nature. The engineered ELPs non-covalently bound to GNs and the resulting ELP-GN hybrids exhibited increased colloidal stability and a reversible temperature-controlled aggregation behavior. The ability of GNs to convert near-infrared light to heat was exploited in order to remotely induce aggregation of ELP-GN hybrids in solution and to induce rapid, site-specific actuation of ELP-GN composite hydrogels. Finally, cell adhesion on ELP-functionalized graphene was enhanced by genetic addition of integrin-binding peptide motifs.

These studies demonstrate that PBPs can be tailored to interact with nanoparticles of choice and can provide stimuli-responsive and bioactive properties to biologically relevant nanoparticles. Hybrid materials of PBPs and nanoparticles are, therefore, well suited for biotechnological applications which require smart behavior.