Emergent Properties and Functions of Nanoconfined Nucleic Acid Architectures

The facile ability of DNA to self-assemble has enabled the creation of complex architectures with diverse functions on surfaces or in solution. This approach provides a powerful design tool for the development of nanoscale devices with transformative applications in multiple areas, including the detection of complex biomolecules, drug delivery, and in situ biomolecular synthesis. However, little is known of the effect of confinement on the function of complex nucleic acid architectures, which exhibit unanticipated behaviors that presumably reflect high-level molecular crowding. In this chapter, we review selected recent studies that describe the application and atypical behaviors of nanoconfined nucleic acids, in particular with respect to hybridization, denaturation, conformation, stability, and enzyme accessibility. We argue that the novel behavior of dense nucleic acid arrays naturally emerge as a result of immobilization and reduction in spatial degrees of freedom. We summarize by emphasizing the need for basic physical–chemical studies of dense nucleic acid architectures, involving an interplay of experimental and theoretical approaches, in order to effectively guide the successful technological development of nucleic acid nanodevices.