Tuning Interfacial Biomolecule Interactions with Massively Parallel Nanopore Arrays

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DNA stores biological information with a very high density. New tools of genomics and genetic engineering that have emerged over the past 20 years, providing the transformative capabilities to both "read" DNA, and to "write" DNA. New biosensors that diagnose diseases and predict responses to treatments can be based on "reading" DNA, and development of new pest-resistant crops, for example, can be based on "writing" DNA. While DNA is protected when inside living cells, it is relatively unstable when exposed to environments outside of cells. This work will advance our understanding of how DNA interacts with a new class of materials with DNA-sized, nanoscale pores. The chemistry of these pores can be tuned to optimize interactions with DNA, for storage, stability, and for reporting specific chemical binding events. In future work, these materials could be used to develop new biosensors and advanced nanomaterials that could store DNA or transduce mechanical and chemical signals through controlled DNA binding. We will study the interactions of short DNA segments with the surfaces and pores of crosslinked protein crystals, by atomic force microscopy and adsorption isotherm measurements. Diffusion of DNA within nanopores will be characterized by fluorescence microscopy methods. Finally, we will assess the ability of protein crystals to: stabilize guest DNA, couple DNA-pore interactions to ligand binding on the protein crystal surface, and report DNA hybridization through fluorescence.