Self-organizing biomaterials using biomolecular networks
Abstract
Project AbstractApproved for public release The overarching goal of this research is to enable the assembly of biomaterials with complex, hierarchical structure using biochemical material assembly programs that regulate their assembly during processes inspired by biological development. These programs, in vitro synthetic genetic regulatory networks (sGRNs), are encoded as and directed by short DNA sequences which are templates from which RNA is transcribed. Transcribed RNA modulates reactions driving biomaterials assembly and also regulates transcription of RNA from other templates. This cross-regulation makes it possible to precisely control the rates and nonlinear dynamics of multiple sGRN outputs and to encode closed-loop feedback, process loops, and decision-making into programs. Biomaterial assembly processes are currently mediated largely by equipment that heats, mixes, or otherwise processes samples. Living cells illustrate how elaborate biomaterial assembly processes can be instead directed by biomolecules such as RNA that modulate interactions between assembling components. Devising processes inspired by this observation could help us overcome current limitations, such as the need for specific equipment and the difficulty of standardizing or optimizing them. These limitations have made it challenging to build biomaterials whose structure that is organized on different length scales, which are critically needed for a range of capabilities, such as directing multistep biochemical syntheses and building synthetic vasculature, soft robots, or opticalor mechanical metamaterials. sGRNs consist of easily synthesized short DNA molecules and a few standard enzymes. The DNA sequencesthat specify sGRN function are, like the text of computer programs, unambiguous and complete descriptions that can be precisely copied to reproduce a process. sGRNs can also be modified and redesigned in silico using models that select modular sequence domains, network elements, andsubnetworks. Recent work has demonstrated how DNA or RNA molecules can trigger an assembly process by activating an assembling species. Here, we will show 1) how sGRNs can orchestrate series of assembly steps and direct parallel reactions by producing multiple RNA outputs each at precise schedules, 2) how sGRNs can direct phase transitions and crystallization by using themto precisely regulate reaction rates, and 3) how reaction-diffusion processes controlled by sGRNs can pattern a material#s structure. Finally, we will show 4) how sGRNs can be a common platform for building many different types of biomolecules by using them to modulate diverse processes such as protein crystallization and biofilm formation. In the near term, this research will create new techniques for reliably producing novel 3-dimensional, multi-component, and multicompartment microparticle, nanoparticle, and syntheticand living cell architectures that act as optical or mechanical metamaterials, synthetic biofilms, or nanofluidic transport networks. Longer-term impacts will arise from the creation here of a common toolkit for precisely specifying and scaling the complexity of biomolecular assembly processes. Such a toolkit will have manifold and profound impacts on DoD capabilities. Just as adopting standardized components and rapid improvements in fabrication technologies together enabled exponential improvements in electrical circuitcomplexity and function at lower costs, the adoption of standard molecular parts that can be combined to build biomolecular circuits for process control and recent exponential decreases in DNA synthesis cost could together catalyze extraordinary improvements the complexity and function of designed hierarchical biomaterials.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 13, 2023
- Source ID
- N000142312868
Entities
People
- Rebecca Schulman
Organizations
- Johns Hopkins University
- Office of Naval Research
- United States Navy