Non-technical: This award by the Biomaterials program in the Division of Materials Research to University of Indiana is to use biological processes and directed self-assembly to make a new generation of materials to overcome their limitations. The investigator sees the biological cell as an inspiration for the design of new complex materials, assembled from molecular components across many different length scales. Currently, even the simplest living systems exhibit complexity that is well beyond the ability to mimic synthetically. The power of biological cells to respond to environmental stress lies in their ability to regulate biochemical networks of enzyme-mediated reactions. Harnessing the power and complexity of enzymes, and enzyme networks, for the synthetic development of complex catalytic materials has not been realized in part due to the fragility of enzymes and their incompatibility with materials processing approaches. This project will develop a set of design rules to incorporate materials properties and catalytic functions to bioinspired materials. This researcher expects these materials to make impacts in areas of bio-designed catalysis and that their utilization will lead to the development of more energy-efficient, renewable, safe and affordable technologies. As an integral part of the project, this investigator will continue to develop science outreach programming wherein undergraduate and graduate students, participating in cutting-edge science, will also learn to effectively communicate their research to the general public and inspire the next generation of scientists. This will be achieved through partnerships with local and regional schools in which long-term relationships between teachers, students, and researchers can foster an excitement about science and connect with youth and communities that are underrepresented in the sciences.
Using a bioinspired approach, this researcher will develop a complex self-assembling system to create protein cage architectures in which multiple copies of up to 3 enzymes are encapsulated with controlled adjacency and stoichiometry. These enzymes perform a coupled cascade of reactions, creating a material capable of effecting a synthetic metabolic pathway for methanol (and potentially methane) oxidation. In addition, a mathematical model is developed for predicting the kinetics for coupled reactions under co-localized conditions, based on the diffusion length of intermediates between partner enzymes. The planned kinetic studies showed that intermediate channeling between sequential enzymes is dependent on both the inter-enzyme distance as well as a balance between the kinetic parameters of the two enzymes, a finding that challenges the simplistic view that any co-localization will automatically yield enhanced overall activities. In addition, individual nanoreactor particles can be assembled into ordered hierarchical arrays providing a path forward for the programmed assembly of bulk materials built from individual protein cages and having designed complex catalytic properties. Thus, using naturally occurring and designed molecular components, the investigator will construct complex catalytically active materials through directed self-assembly of modular building blocks at multiple lengthscales. Graduate student training in the context of this research will include: structural studies using cryo-electron microscopy and image reconstruction to evaluate the packing of enzymes within the self-assembled protein cage architectures; mass spectrometry to evaluate changes in enzyme dynamics due crowding effects; dynamic and static (multi-angle) light scattering to evaluate the self-assembly processes from molecular components to materials; small angle x-ray scattering (Argonne National lab (APS) and Brookhaven National Lab (NSLS II) to probe the long range order in the assembly of protein cage materials. The students will be trained in the relevant characterization techniques.
