Protein framework for manipulating nanoparticles and enzymes: from capsules to arrays

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Professors Ivan J. Dmochowski and Jeffery G. Saven of the University of Pennsylvania are supported by the Macromolecular, Supramolecular and Nanochemistry Program of the Division of Chemistry to elucidate how hollow and cage-like proteins can form nano-containers to encapsulate nanoparticles and other proteins such as enzymes. Experimental approaches and theoretical methods are combined to understand these molecular systems and to engineer molecular containers for specific cargos and applications. An important aim of the project is to develop chemistries and methods to link single containers together to form three-dimensional microarray structures. The goal is to engineer microarrays for specific applications in catalysis, and to integrate judicially designed microarrays in functional devices, such as biosensors and enzyme cargo delivery systems. Cage-like ferritin proteins provide a unique model system for studying bio-nano supramolecular assembly, and the modular "molecular capsule-to-array" concept provides a versatile platform for addressing many materials chemistry challenges in nanotechnology and biotechnology. Ordered hierarchical assembly of small nanostructures into larger, well-structured arrays can deliver desirable materials properties, self-assembly, and processability. Graduate and undergraduate students, including students from the University of Puerto Rico, are receiving multidisciplinary training through this collaborative research. In addition, laboratory and classroom activities targeting middle, and high school students are being developed. These activities are subjected to evaluation and best practices are prepared for publication in chemical education journals.Ferritin proteins encapsulate appropriately sized and liganded inorganic nanoparticles or super-positively-charged proteins in native-like assemblies. The research team aims to elucidate how cage-like proteins, such as thermophilic ferritin from A. fulgidus (AfFtn), encapsulate various nonbiological and biological cargo to form stable, molecularly precise nano-containers. Computational protein design identifies amino acid mutations that enhance the stability of ferritin capsules. Design and modeling are also applied to guest species, such as super-positively-charged enzymes, to explore determinants of efficient ferritin encapsulation. Molecular simulations provide insight on the structure and dynamics of ferritin-nanoparticle and ferritin-protein interactions. Guided by computational design, an expanded set of inorganic nanoparticles and enzyme cargos are being identified and assessed. Experimental approaches range from the creation and processing of recombinant proteins to the biophysical characterization of ferritin assembly and encapsulation in solution and in the solid-state. An important goal is to link AfFtn capsules at engineered and structurally well-determined attachment sites to form well-defined arrays. Among several strategies to be pursued is the incorporation of divalent cation binding sites at the three-fold symmetric ferritin pores and subsequent formation of arrays with bis-hydroxamate linkers.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.