Non-Technical Abstract: Biochemical reactions in organisms and in numerous sensing and manufacturing applications are controlled by a special type of biomolecule, the enzyme. While there is a great demand for the design of new types of enzymes with enhanced properties, it is a very challenging task that requires enormous computational and synthetic efforts. There is another way to enhance the chemical activity of enzymes and to allow for a much more convenient use of them - by packaging these biomolecules in arrays. Such packaging also opens up the possibility of handling and processing enzymes similar to conventional materials. Until now, enzymatic arrays have been formed by attaching enzymes to surfaces. These enzyme-coated surfaces are used in biosensing to boost sensitivity, thanks to a much higher density of enzymes on a surface relative to in solution. They are also extremely useful for industrial chemical synthesis due to their ability to enhance reactions and how easily they can be integrated into the manufacturing processes. However, current methods to fabricate such enzymatic arrays are limited to surface-based forms. The proposed research aims to establish a conceptually different approach to create three-dimensional (3D) enzymatic arrays in the form of a bulk material rather than a surface. The proposed approach offers nanoscale control over the spatial arrangement and composition of 3D enzymatic arrays. Such arrays represent a new class of chemical materials with tailorable structure, and with modulated and enhanced reactivity. The proposed program seeks to address two key questions in creating these new enzymatic materials: how to synthesize the chemically active materials with control of their structure in 3D, and how to improve the chemical performance of enzymes through the use of novel 3D arrays. The proposed research aims to establish transformative capabilities in the area of designed chemical nanomaterials with potential applications in biosensing, reaction management, and chemical synthesis.
ability to organize enzymes and enzymatic cascades in three-dimensions (3D) with a nanoscale control over the placement of individual enzymes can open new routes for creating chemically active materials and modulating reaction pathways. However, establishing such capabilities presents a significant challenge. The proposal seeks developing a versatile methodology to program assembly of enzymes, guided by DNA frames, into tailored 3D ordered arrays of nanoreactors with control over lattice type, unit cell spacing, ratio of individual enzymes, and relative layout of the chemically active materials. The proposed studies will apply new levels of structure organization of enzymes and enzymatic cascades into desired 3D organizations. Using model enzymatic cascades, the research will explore catalysis within a 3D network and effects of its modification by controlling local chemical environments of enzymes and a global structuring of nanoreactor arrays. The research program will integrate efforts in synthesis of DNA-enzyme modules and their assembly into 3D materials with structural and chemical analysis of formed arrays for exploration of the novel 3D catalytic networks. Synergistic network effects stemming from large scale, 3D organization of enzymes and ease of molecular transport though 3D arrays will be explored. The major objectives of the program include: (i) tailored control over 3D nanoreactor arrays; (ii) determination of local effects arising from enzyme-DNA integration and enzyme colocalizations in 3D; (iii) development of full spatial control over fabrication enzymatic materials, such as crystal system of nanoscale arrays, inter-enzyme spacing, ratio of enzymes, and nanoscale organization of cascades within arrays. The research aims to establish new methods for synthesis of novel classes of 3D nanoreactor arrays, to elucidate the structure-function relationship of networked chemical reactions and to develop ways for manipulating chemical pathways.
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.
