Programming energy landscapes for absolute molecule positioning and robust molecular computation

Synopsis

How do you 'program' an energy landscape so that DNA-based devices follow designed reaction pathways, yet incur significant kinetic and thermodynamic energy penalities for spurious pathways? I'll focus on two different projects butting up against this same theme in different ways. (Part I) A very successful example of self-assembly, driven by molecular forces, is DNA origami. This process can result in the assembly of ~10^10 copies of a designed 2D or 3D shape, with feature resolution of 6 nanometers. Efforts have sought to place these DNA origami on a surface by creating a regular lattice of patches, via ebeam lithography, to which the origami could bind. Origami can initially land (from solution) onto the surface in any orientation or translation relative to a patch, and the electrostatic force between patch and origami, coupled with stochastic perturbation, drives a process to improve the binding between the pair. To ensure an origami cannot become 'stuck' in a degenerate placement, the energy landscape exhibited by the patch-origami pair should have the following property: from all initial placements there should exist a path, to one or more of the designated final placements, that monotonically increases the number of chemical bonds between the origami and surface. We give such a patch-origami pair and demonstate orientation that is absolute (all degrees of freedom are specified) and arbitrary (every molecule's orientation is independently specified). (Part II) The most sophisticated molecular computing systems have been built upon the DNA strand displacement (DSD) primitive, where a soup of rationally designed nucleotide sequences interact, react, and recombine over time in order to carry out complex computation. Existing systems are often slow, error-prone, require bespoke design and weeks of effort to realize experimentally. We demonstrate that it's possible to design and experimentally realize fast, sophisticated and robust molecular circuits in the course of an afternoon. This builds on our theoretical work which shows that by designing DSD systems with increased redundancy N, even at thermodynamic equillibrium, unintended signal production is descreased exponentially with N.