Connecting localized DNA strand displacement reactions

Abstract

Logic circuits based on DNA strand displacement reactions have been shown to be versatile enough to compute the square root of four-bit numbers. The implementation of these circuits as a set of bulk reactions faces difficulties which include leaky reactions and intrinsically slow, diffusion-limited reaction rates. In this paper, we consider simple examples of these circuits when they are attached to platforms (DNA origamis). As expected, constraining distances between DNA strands leads to faster reaction rates. However, it also induces side-effects that are not detectable in the solution-phase version of this circuitry. Appropriate design of the system, including protection and asymmetry between input and fuel strands, leads to a reproducible behaviour, at least one order of magnitude faster than the one observed under bulk conditions.

Design and analysis of linear cascade DNA hybridization chain reactions using DNA hairpins

“…At 5 nM concentration, our LCR system leak occurs at a slower rate than the actual reaction as shown in figure 5(A). An alternative approach to conquer leak is (i) to tether DNA systems on a surface of DNA nanostructures [63,64,[69][70][71][72], or (ii) to incorporate double or triple length domain motifs [73]. Note that the fluorescence data for leaks at 50 nM indicates quite significant leaks as compared to the gel data for leaks at 500 nM of the same system at equilibrium in figure 3(A) lane 3.…”

DNA Nanodevices Confined on DNA Origamis: an Isothermal Ratchet Driven by Boundary Conditions

“…In diluted solution the device can be perfectly symmetric as it happens with the seesaw gates [9], while when the device is tethered on origamis, a highly asymmetric structure is generated through the hybridisation of a fraction of the strands on the origamis [23]. A highly asymmetric structure generates several interesting results, for instance we got the main result that whatever the toe hold strength is the logical operation always succeeds [27,30] (see figure 6).…”

“…Then an abrupt change occurs and the output strand diffuses away. In a recent paper we reported experimental results of DNA computation with DNA nanodevices tethered on origamis [23]. The aim was to amplify an input signal with four output gates and fuel strands.…”

“…This is a complex problem and the reason why we adopt a reductionist approach, with which we hope we could extract some basic principles. Based on the numerous previous works [24,25,26] and our recent experimental results and analysis investigating the behaviour of DNA nanodevices on origamis [23,27], the present work is an attempt to improve our understanding of the head motion of a single strand pushing and removing another almost identical one that already forms a duplex with its complementary single strand. Such a chemical reaction can be seen as a race competition between two identical, or slightly different runners, running in opposite direction along a 1 dimensional energy landscape.…”

“…In both cases, these two significant advantages increase the capacity and complexity of the computation and its robustness. To exploite those advantages, we recently did work using DNA nanodevices tethered on origami templates [23] using the toe hold strand displacement technique [24,25,26]. While it is a convenient way to construct modular Boolean operations with a sequence of chemical reactions, it happens that the use of the strand displacement in diluted and confined environment rises new questions.…”