Handhold-mediated strand displacement: a nucleic acid based mechanism for generating far-from-equilibrium assemblies through templated reactions.
Author(s)
Cabello-Garcia, Javier
Bae, Wooli
Stan, Guy-Bart V
Ouldridge, Thomas E
Type
Journal Article
Abstract
The use of templates is a well-established method for the production of sequence-controlled assemblies, particularly long polymers. Templating is canonically envisioned as akin to a self-assembly process, wherein sequence-specific recognition interactions between a template and a pool of monomers favor the assembly of a particular polymer sequence at equilibrium. However, during the biogenesis of sequence-controlled polymers, template recognition interactions are transient; RNA and proteins detach spontaneously from their templates to perform their biological functions and allow template reuse. Breaking template recognition interactions puts the product sequence distribution far from equilibrium, since specific product formation can no longer rely on an equilibrium dominated by selective copy-template bonds. The rewards of engineering artificial polymer systems capable of spontaneously exhibiting nonequilibrium templating are large, but fields like DNA nanotechnology lack the requisite tools; the specificity and drive of conventional DNA reactions rely on product stability at equilibrium, sequestering any recognition interaction in products. The proposed alternative is handhold-mediated strand displacement (HMSD), a DNA-based reaction mechanism suited to producing out-of-equilibrium products. HMSD decouples the drive and specificity of the reaction by introducing a transient recognition interaction, the handhold. We measure the kinetics of 98 different HMSD systems to prove that handholds can accelerate displacement by 4 orders of magnitude without being sequestered in the final product. We then use HMSD to template the selective assembly of any one product DNA duplex from an ensemble of equally stable alternatives, generating a far-from-equilibrium output. HMSD thus brings DNA nanotechnology closer to the complexity of out-of-equilibrium biological systems.
Date Issued
2021-02-23
Date Acceptance
2021-01-14
Citation
ACS Nano, 2021, 15 (2), pp.3272-3283
ISSN
1936-0851
Publisher
American Chemical Society
Start Page
3272
End Page
3283
Journal / Book Title
ACS Nano
Volume
15
Issue
2
Copyright Statement
© 2021 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsnano.0c10068
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Royal Academy Of Engineering
Commission of the European Communities
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33470806
Grant Number
EP/P02596X/1
CiET1819\5
851910
Subjects
fluorescence
kinetics
nucleic acids
reaction mechanism
self-assembly
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2021-01-20