Self-Assembled Protein Cage Nanoreactors

Indiana University, Bloomington IN

Investigators

Abstract

ID: MPS/DMR/BMAT(7623) 1104849 PI: Douglas, Trevor ORG: Montana State University Title: Self-Assembled Protein Cage Reactors INTELLECTUAL MERIT: Protein shells that sequester enzymatic reactions are found in diverse organisms and may provide blueprints for functional biomaterials design. The aim of this proposal is to design and develop a new class of bio-inspired materials utilizing the directed confinement of enzymes within viral protein cage assemblies. This is a powerful strategy for combining biological supramolecular architectures with catalytic function. While the encapsulated enzymes retain their native catalytic activity the protein cage can be separately optimized as a container that can shield the enzymatic cargo from its environment, enhance stability, and modulate enzymatic activity. Viruses have emerged as transformational and significantly useful materials and the PI has been a leader in the development of this field. The proposed research will enhance the use of viral capsids for synthetic applications of bioactive materials. Such materials will dramatically extend biotechnology's range of applications, allowing biocatalysts to be used in contexts very different from their evolved cellular role. This work will further the use of biological systems for the inspiration, design, and synthetic implementation of functional materials. The specific aims of this work are to: (1) develop programmed co-assembly of a viral capsid with a range of enzymatic cargos including lactonases for disruption of quorum sensing in bacterial biofilms, (2) evaluate the effects of molecular crowding on the activity of the encapsulated enzymes, and (3) co-assemble multiple enzymes into the viral capsids that can chemically communicate with each other to create bio-inspired nanoscale reactors. The enzymes of interest have been selected for their extreme thermal stability commensurate with their use as materials building blocks. In addition, this effort will train a diverse group of graduate and undergraduate students in this inherently green chemistry approach to nanomaterials synthesis that incorporates the remarkable materials properties already utilized by nature. BROADER IMPACTS: This research has the potential to enable significant progress in the emerging fields of biomaterials, nanotechnology, and nano-manufacturing. Biological control mechanisms used by natural systems will be exploited to create novel materials and devices exhibiting genetically programmed synthesis in a biomimetic approach to making functional materials. The abundance and unique qualities of these new viral materials will enable researchers to develop new active bio-materials. Integral to this project is an innovative science outreach program developed by the PI that creates meaningful outreach experiences where undergraduate and graduate students learn to communicate effectively their research and their passion for science. The outreach infrastructure that has been developed and piloted provides a template for faculty and students to effectively share their interest in science through hands-on, inquiry-based events. Outreach events will take place in K-12 local public schools and with rural and predominantly Native American schools. They include site visits as well as hosting on-campus events. The fundamental goal of this outreach program is to place active researchers in the front line of community interaction. These events ultimately result in basic science exploration, introduction to current research trends and local projects, and most importantly, contact with active researchers who become role models and recruiters of the next generation of learners.