Nanomanufacturing of Protein Macromolecular Frameworks Through an Integrated Bioengineering and Computational Approach

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New materials with innovative functionalities are needed to build new and useful devices and systems that enrich our lives. Ordered three-dimensional arrays built from nanoscale building-blocks, often called superlattices, are exciting because new functionalities can emerge from the interactions between individual building-blocks. The use of proteins as building-blocks is a groundbreaking new direction because proteins exhibit a wide range of properties and behavior, including catalytic and immune activities, which are often difficult to realize in synthetic molecules. Making ordered materials by conventional protein crystallization is a laborious procedure and the ability to tailor the structure of protein crystals is limited. This award supports fundamental research to develop versatile and tunable approaches to manufacture superlattice materials constructed of proteins. The availability of these unique protein-based materials impacts diverse industries such as energy, biomedical and catalysis, which advances national welfare. This project uniquely integrates several disciplines including materials science, bioengineering and computational modeling. The integration of experimental and computational approaches in this project impacts research efforts of the Network for Computational Nanotechnology (NCN), synergistically. Alongside the scientific impact of the project, it also leverages the multi-disciplinary approach to promote students, including women and minorities, on this project by acquiring broad skills and knowledge and by providing a positive impact on science education.The research team envisions that protein cage nanoparticles and linker proteins, which bind non-covalently to symmetry-specific sites on the protein cages, are promising building-blocks for constructing a new class of protein superlattices, i.e. protein macromolecular frameworks. Protein cages have hollow spherical architectures composed of a distinct number of subunits with well-defined symmetry-specific sites. The investigators anticipate that specific binding geometries between protein cages and linkers result in highly regular network structures with a wide range of functionalities. The research team integrates bioengineering and computational modeling approaches to develop a range of linker molecules with different lengths and binding affinities to protein cages. By connecting the protein cages together through protein linkers, they are geometrically confined, thus forming highly regulated structures. The structure of the protein macromolecular frameworks is tunable through the selection of protein cages and specific linker proteins. Additionally, protein macromolecular frameworks have two types of unique spaces internally to accommodate cargo molecules. These are interior cavity of individual protein cages and interstitial space between protein cages within the lattice. The team demonstrates that various cargo molecules, such as enzymes, could be encapsulated inside of the protein cages. In this project, reversible incorporation and release of guest molecules are studied, which could lead protein macromolecular frameworks to practical applications such as drug delivery and catalysis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.