Determining the rules for designing active DNA materials with condensing agents

About This Grant

NON-TECHNICAL SUMMARY: DNA is the molecule in your cells that stores your genetic information, but it is also an important building material on the nanoscale. The base-pairing rules of DNA—A binds to T, C binds to G—allow engineers to easily assemble different shapes and structures. However, the simplicity of DNA also limits its functionality. By adding particular molecules called condensing agents to DNA, our goal is to bend, loop, stack, or reconfigure DNA on command. This reconfiguring of the DNA could impart dramatic properties to the DNA material, including decreased size, increased stability, increased stiffness, decreased permeability, or increased electrical conductivity. We will study three questions: How do condensing agents bend and loop DNA? How do condensing agents reconfigure DNA? And, how can we use condensing agents to engineer particular DNA materials? Answers to these questions will impact our use of DNA materials in various applications, including immunotherapies, carbon capture technology, tissue engineering, biosensing, or nanorobotics. More broadly, the science in the grant will be driven entirely by undergraduate researchers, presenting an incredible educational opportunity to train the next generation of scientists and engineers. At the same time, the training modules created by the undergraduates will then be used to train college/university instructors in a nationwide program. TECHNICAL SUMMARY: DNA is a ubiquitous biomaterial that is easy to engineer. However, this simplicity limits functional versatility. Here, we will use a biomimetic approach and couple DNA to the condensing agents, which typically fold, loop, condense, or reconfigure the DNA inside the cell. Condensing agents are a class of positively charged molecules that could be used to self-assemble and reconfigure DNA materials on cue, creating increased condensation, increased stability, increased stiffness, decreased permeability, or increased electrical conductivity. Our goal is to determine the rules for how condensing agents bend, loop, condense, and reconfigure DNA molecules and DNA assemblies. While researchers have been studying how condensing agents condense DNA for 40 years, the answers still remain elusive. We will use new single molecule techniques, as well as a “bottom-up” approach, starting with short DNA molecules and working up to larger DNA assemblies, to study the structures, pathways, mechanics, and energetics of the process. In addition, we will—for the first time—look at how condensing agents reconfigure DNA molecules with several assembled nucleosomes. This project will pave the way for DNA biomaterials with exquisite regulatory, electrical, mechanical, or geometric control. This work will be driven entirely by undergraduate researchers, presenting an incredible educational opportunity to train the next generation of scientists and engineers. Training modules created by the undergraduates will then be used to train college/university instructors in a nationwide program. 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.