Analysis and Control of Self-Assembling Nucleic Acid Systems

The specificity and predictability of Watson-Crick base pairing has been exploited to direct the assembly of oligonucleotides into myriad structures, chemical logic circuits, walkers and machines. However, we have only recently begun to develop and test models capable of describing the self-assembly processes. We previously introduced hybridization chain reactions (HCR), in which metastable DNA hairpins undergo conditional self-assembly to form long nicked double-stranded ‘polymers' in the presence of a DNA initiator molecule (PNAS 2004, 10, 15275). Here, we model the equilibrium and kinetic properties of HCR, revealing sources of non-ideal behavior and methods for controlling system performance. Our results demonstrate that upon initiation, HCR is accurately modeled as a living alternating copolymerization.