Abstract
We present a modular DNA origami design approach to address the challenges of
assembling geometrically complex nanoscale structures, including those with
nonuniform Gaussian curvature. This approach features a core structure that
completely conserves the scaffold routing across different designs and
preserves more than 70% of the DNA staples between designs, dramatically
reducing both cost and effort, while enabling precise and independent
programming of subunit interactions and binding angles through adjustable
overhang lengths and sequences. Using cryogenic electron microscopy, gel
electrophoresis, and coarse-grained molecular dynamics simulations, we validate
a set of robust design rules. We demonstrate the method's utility by assembling
a variety of self-limiting structures, including anisotropic shells with
controlled inter-subunit interactions and curvature, and a toroid with globally
varying curvature. Our strategy is both cost-effective and versatile, providing
a promising and efficient solution for the synthetic fabrication of complex
nanostructures.