Programmable 2- and 3-Dimensional Protein Assemblies

University Of California-San Diego, La Jolla CA

Investigators

Abstract

Nontechnical: Under this award from the Biomaterials Program in the Division of Materials Research to University of California-San Diego, the researcher will develop new chemical approaches for the design and engineering of novel protein assemblies. This award is co-funded by the following programs: 1) BioMaPS program in the Division of Materials Research; and 2) Biotechnology and Biochemical Engineering program in the Division of Chemical and Bioengineering, Environmental, and Transport Systems (ENG). Proteins are nature's premier building blocks in constructing complex biological systems such as the photosynthetic machinery or for building sophisticated materials with advanced physical and chemical properties such as the human skin and bone. However, proteins are remarkably complex molecules with non-uniform surfaces and structures, and the ability to control the self-assembly of proteins or to use them as synthetic building blocks has been limited. In this project, the assembly of supramolecular protein architectures will be studied by using new approaches of chemical bonding and self-assembly strategies that are expected to give rise to new classes of synthetic protein assemblies. Such an ability to construct complex biological structures in a bottom-up fashion from multiple components will not only provide fundamental insights into biological self-assembly processes, but will also lend access to novel protein-based functionalities and materials with potential applications in bio/nanotechnology and biomedical applications such as drug/gene transport and tissue regeneration. As part of the teaching and training, this project will provide training for postdoctoral, graduate, undergraduate, and high school researchers in supramolecular chemistry, molecular biology, protein biochemistry, crystallography, biophysical techniques, and computational protein design. The PI's outreach efforts will be expanded on several different fronts, including active recruitment of members of underrepresented minority groups for research. High school students will be recruited through various self-initiated and campus-supported programs, and with involvement in science fairs at local elementary schools. Technical: This multidisciplinary project is based on the application of supramolecular chemistry principles, protein engineering and molecular biology to the study and control of protein self-assembly. Protein building blocks with appropriately chosen structures/symmetries will be designed to assemble into prescribed supramolecular assemblies through disulfide bonding, electrostatic and designed surface interactions. The main goal of this project is to expand the capability to construct supramolecular protein architectures by utilizing non-inorganic modalities of chemical bonding and self-assembly strategies that circumvent the need for designing extensive interfaces. This goal will be accomplished through three objectives: 1) in developing molecular design strategies for the disulfide-directed assembly of homomeric, 2 and 3-D protein arrays and architectures; 2) in implementing auxiliary interactions and surface-templating strategies for improved control of disulfide-directed protein assembly; and 3) in constructing DNA-directed 2- and 3-D crystalline protein arrays. Physical, biochemical and structural properties of these assemblies will be characterized by a large suite of techniques including electron microscopy and diffraction, atomic force microscopy, protein crystallography, and solution biophysical methods. The resulting protein architectures and hybrid materials could be utilized for materials applications such as templating of inorganic nanoparticles and encapsulation of various types of molecular cargos. The proposed activities would expand the current understanding for designing highly ordered 2 and 3D protein nanostructures from the bottom up, and would likely aid a broad range of researchers in building protein-based nanomaterial structures. The researcher has an impressive track record in recruiting and mentoring underrepresented minority students in research activities, and plans are provided to expand these activities.