Renewable DNA seesaw logic circuits enabled by photoregulation of toehold-mediated strand displacement

Abstract

An important achievement in the field of DNA-based computation has been the development of experimental protocols for evaluation of Boolean logic circuits. These protocols for DNA circuits generally take as inputs single-stranded DNA molecules that encode Boolean values, and via a series of DNA hybridization reactions then release ssDNA strands to indicate Boolean output values. However, most of these DNA circuit protocols are use-once only, and there remains the major challenge of designing DNA circuits to be renewable for use with multiple sets of inputs. Prior proposed schemes to make DNA gates renewable suffered from multiple problems, including waste accumulation, signal restoration, noise tolerance, and limited scalable complexity. In this work, we propose a scalable design and in silico verifications for photoregulated renewable DNA seesaw logic circuits, which after processing a given set of inputs, can be repeatedly reset to reliably process other distinct inputs. To achieve renewability, specific toeholds in the system are labeled with photoresponsive molecules such as azobenzene to modulate the effective rate constants of toehold-mediated strand displacement (TMSD) reactions. Our proposed design strategy of leveraging the collective effect of TMSD and azobenzene-mediated dehybridization may provide new perspectives on achieving synchronized and localized control of DNA hybridizations in complex and scalable reaction networks efficiently and economically. Various devices such as molecular walkers and motors could potentially be engineered reusable, be simulated and subsequently implemented using our simplified design strategy.

Photoresponsive Self‐Assembled DNA Nanomaterials: Design, Working Principles, and Applications

“…Among a number of photoisomerizable molecules, azobenzene and its derivatives are the most popular phototrigger for versatile applications because of: 1) simple chemical synthesis; 2) high chemical stability between repeated trans ‐ and cis ‐photoisomerization in aqueous conditions; 3) high feasibility of the conformational change in a densely packed DNA system. By looking at the chemical structure of azobenzene, it contains a NN double bond, which connects the two phenyl moieties in specific configuration ( Figure ) . When azobenzene molecules were intercalated at specific positions on DNA duplex, its helical binding stability could be easily disturbed by the polarity and conformational change of azobenzene under sequential irradiation of UV and visible light.…”

“…Schematic diagram of azobenzene isomerization triggered by light irradiation which results in a conformational change with high speed, making an azobenzene molecule undergoing transition of two configurations. Adapted with permission . Copyright 2017, the Authors, published by The Royal Society of Chemistry.…”

“…(5) Gate reversal: the end product after the strand displacement with cis ‐azobenzene. Reproduced with permission . Copyright 2017, The Royal Society of Chemistry.…”

“…More recently, Reif's group has built a toehold‐mediated strand displacement DNA logic circuit with the limited use of azo‐modified DNA strands to furnish its reusability and renewability . At the initial state, a DNA strand was added as first input to trigger the strand displacement reaction in the DNA system as shown in Figure B‐(1),(2).…”

Devices for safety-critical molecular programmed systems

“…Interest in the field began growing when Winfree proved the Turing universality of the model [66]. Many advancements have appeared in the field in years since, from Boolean circuits [7,57,62], to DNA based nano-robots [6,12], to devices that contain drugs for delivery to targeted cells [15,67,44].…”