Abstract
Molecular programming takes advantage of synthetic nucleic acid biochemistry to assemble networks of reactions, in vitro, with the double goal of better understanding cellular regulation and providing information-processing capabilities to man-made chemical systems. The function of molecular circuits is deeply related to their topological structure, but dynamical features (rate laws) also play a critical role. Here we introduce a mechanism to tune the nonlinearities associated with individual nodes of a synthetic network. This mechanism is based on programming deactivation laws using dedicated saturable pathways. We demonstrate this approach through the conversion of a single-node homoeostatic network into a bistable and reversible switch. Furthermore, we prove its generality by adding new functions to the library of reported man-made molecular devices: a system with three addressable bits of memory, and the first DNA-encoded excitable circuit. Specific saturable deactivation pathways thus greatly enrich the functional capability of a given circuit topology.
Highlights
Molecular programming takes advantage of synthetic nucleic acid biochemistry to assemble networks of reactions, in vitro, with the double goal of better understanding cellular regulation and providing information-processing capabilities to man-made chemical systems
One can build networks made of chemical reactions, where each node is a particular DNA molecule or complex and where edges represent their kinetic relationships
The PEN DNA toolbox (Polymerase/Exonuclease/Nickase Dynamic Network Assembly toolbox) is a set of chemical reactions that has led to some advanced experimental demonstrations[30,31,34,35]
Summary
Molecular programming takes advantage of synthetic nucleic acid biochemistry to assemble networks of reactions, in vitro, with the double goal of better understanding cellular regulation and providing information-processing capabilities to man-made chemical systems. The PEN DNA toolbox (Polymerase/Exonuclease/Nickase Dynamic Network Assembly toolbox) is a set of chemical reactions that has led to some advanced experimental demonstrations[30,31,34,35] It is fuelled by dNTPs, based on enzymatic DNA polymerization/ depolymerization steps and uses only two generic modules encoded by short single-stranded DNA templates (20–30 bases long): the first one, ‘activation’, mimics the basic stimulation of gene expression by a single transcription factor, while the second one, ‘inhibition’, emulates the converse, inhibitory process. The benefit of nonlinearities for in vitro molecular programs was demonstrated with ‘genelet’ circuits, where an intermediate circuitry between the active elements can be harnessed to adjust thresholds This titration-based approach led to compact bistable or oscillating networks[6,7,15]
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