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DE-SC0019752: Programmable Dynamic Self-Assembly of DNA Nanostructures

Award Status: Active
  • Institution: Regents of the University of California, Los Angeles, Los Angeles, CA
  • DUNS: 092530369
  • PM: Markowitz, Michael
  • Most Recent Award Date: 06/12/2019
  • Number of Support Periods: 1
  • PI: Franco, Elisa
  • Current Budget Period: 06/15/2019 - 06/14/2020
  • Current Project Period: 06/15/2019 - 06/14/2022
  • Supplement Budget Period: N/A
 

Public Abstract


The synthesis of novel materials with sustained dynamic behaviors akin to those of biological cells is a central challenge in biomolecular materials research. In cells, behaviors such as growth, motility, and self-repair emerge from the concerted operation of self-assembling components, sensing and control systems, and energy conversion and storage processes. The goal of this project is to construct synthetic materials with a similarly organized structure, that is, where the capacity for adaptive, dynamic responses is achieved by coordinating synthetic self-assembly processes with synthetic molecular circuits that fuel and regulate assembly.         

In the current and previous award periods, we have developed methods to program the dynamics of assembly and disassembly of DNA-based materials that demonstrated the power of systematic methods for the design of multicomponent, coupled biomolecular materials systems. We have created a toolkit of rationally designed DNA components to build dynamic materials that can respond to stimuli and to non-equilibrium nucleic acid signals generated by circuits and sensors.  We then demonstrated how materials built from these components and circuits can display quantitatively new forms of dynamics and adaptive organization. DNA-based materials are a versatile laboratory for programming and understanding dynamic behavior of self-assembling systems, because their thermodynamics and kinetics are well understood and it is possible to couple DNA nanostructure assembly processes to molecular circuits, allowing systematic manipulation of assembly over time or in response to environmental signals.  As such, the design of coupled systems of reactions for DNA self-assembly can serve as a blueprint for the design of other advanced bio-inspired materials systems.  

Our goal in the next funding cycle is to identify design principles that make it possible to engineer sustained and kinetically controlled behaviors in our materials, making it possible to scale the complexity of the dynamics that may be programmed in these systems. To do so, we will develop new methods to manage the storage and release of molecular fuel species, so that assembly reactions can be dynamically regulated for long periods of time; these methods include buffering circuits, feedback, and compartmentalization. We will then explore how the use of these fueling systems can lead to advanced DNA-based and DNA-directed dynamic, multi-component materials to achieve complex chemomechanical behaviors that include topological reconfiguration of complex DNA nanotube networks, spatiotemporal control of network assembly based on fuel gradients, and stimulus-controlled growth of linear nanotube fibers.  Achieving such behaviors will require the application of fundamental ideas from systems engineering and control theory, including modular organization, standardization of interactions between components and the application of feedback to achieve robust adaptation and control of dynamics.

This research endeavor is directed toward BES Basic Research needs: it seeks to identify mechanisms by which it is possible to engineer systematically new self-assembling materials with the capacity for adaptive responses that can increase their resilience. This work integrates advanced coarse-grained modeling techniques for complex biomaterials, theoretical methods from dynamical systems research, and systematic and quantitative experimentation and measurement of material dynamics and structure to achieve these goals.





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