(3el) Multifunctional Protein-Based Materials for the Synthesis and Organization of Nanomaterials

Recent advances in materials synthesis have revealed unique properties that occur at the nanoscale; however, the long-range organization of nanomaterials into the hierarchical structures required for applications remains an unmet challenge. In striking contrast, such hierarchical organization is an integral feature of natural bioinorganic materials, where the concerted action of proteins exquisitely orchestrates structural organization. One of the key challenges in protein-based synthesis of inorganic materials is developing robust and versatile strategies for a chosen protein scaffold to interact with inorganic components in a specific and controlled manner. In my PhD thesis research, I have developed a new biomimetic strategy to modify protein scaffolds based on site-specific molecular recognition. This versatile strategy, termed Template Engineering Through Epitope Recognition (TEThER), is based on the design of bi-functional TEThER peptides that mimic the activity of natural adaptor proteins to site-specifically assemble with a single native protein scaffold for a variety of functions.

This project focused on understanding the unique self-assembling protein clathrin and developing the TEThER strategy to modify self-assembled clathrin scaffolds for the synthesis of inorganic nanomaterials. The self-assembly of clathrin was studied through a combination of dynamic light scattering and cryo transmission electron microscopy which showed it to be a highly dynamic process that can progress through different kinetic pathways to arrive at ordered three-dimensional structures. By designing a family of TEThER peptides, I have demonstrated the versatility of the novel site-specific method TEThER strategy to bridge the interface between self-assembled clathrin and two classes of inorganic materials, metal oxides and noble metals, to synthesize titanium dioxide, cobalt oxide, and gold nanoparticles. Crystallographic characterization of nanoparticle morphology and phase using transmission electron microscopy gives insight into the nucleation and growth mechanism for each of these reactions. Peptide sequences with affinity for various inorganics can be combined with site-specific recognition sequences for other clathrin scaffold binding sites in a mix-and-match manner to enable the nucleation and growth of a wide variety of materials and nanoscale patterns. Additionally, since this strategy is based on molecular recognition that occurs at protein binding interfaces, it is broadly applicable to other protein systems.

In my research program I aim to develop multifunctional protein-based materials for the synthesis and long-range organization of nanomaterials through self-assembly and the design and use of multi-component, modular systems. Such a strategy offers a promising new way forward for the manipulation and organization of materials at the nanoscale. Through continued development of strategies to interface a variety of native and engineered biomolecules with inorganic materials, the bottom-up synthesis of designed hierarchically-ordered biomimetic nanomaterials for applications such as energy conversion and storage and bone tissue regeneration will be possible. My interdisciplinary background uniquely positions me to accomplish this goal by bringing together insight from diverse fields, including materials science, protein engineering, and chemistry.