  Nucleation is the rate-determining step in the kinetics of many self-assembly
processes. However, the importance of nucleation in the kinetics of DNA-origami
self-assembly, which involves both the binding of staple strands and the
folding of the scaffold strand, is unclear. Here, using Monte Carlo simulations
of a lattice model of DNA origami, we find that some, but not all, designs can
have a nucleation barrier and that this barrier disappears at lower
temperatures, rationalizing the success of isothermal assembly. We show that
the height of the nucleation barrier depends primarily on the coaxial stacking
of staples that are adjacent on the same helix, a parameter that can be
modified with staple design. Creating a nucleation barrier to DNA-origami
assembly could be useful in optimizing assembly times and yields, while
eliminating the barrier may allow for fast molecular sensors that can
assemble/disassemble without hysteresis in response to changes in the
environment.
