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  1. Abstract

    Chemical systems have the potential to direct the next generation of dynamic materials if they can be integrated with a material while acting as the material’s own regulatory network. Chemical networks that use DNA and RNA strand displacement coupled with RNA synthesis and degradation, such as genelets, are promising chemical systems for this role. Genelets can produce a range of dynamic behaviors that respond to unique sets of environmental inputs. While a number of networks that generate specific types of outputs which vary in both time and amplitude have been developed, there are fewer examples of networks that recognize specific types of inputs in time and amplitude. Advanced chemical circuits in biology are capable of reading a given substrate concentration with relatively high accuracy to direct downstream function, demonstrating that such a chemical circuit is possible. Taking inspiration from this, we designed a genelet circuit which responds to a range of inputs by delivering a binary output based on the input concentration, and tested the network’s performance using an in silico model of circuit behavior. By modifying the concentrations of two circuit elements, we demonstrated that such a network topography could yield various target input concentration profiles to which a given circuit is sensitive. The number of unique elements in the final network topography as well as the individual circuit element concentrations are commensurate with properties of circuits that have been demonstrated experimentally. These factors suggest that such a network could be built and characterized in the laboratory.

     
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    Free, publicly-accessible full text available June 20, 2025
  2. Characterizing the relative onset time, strength, and duration of molecular signals is critical for understanding the operation of signal transduction and genetic regulatory networks. However, detecting multiple such molecules as they are produced and then quickly consumed is challenging. A MER can encode information about transient molecular events as stable DNA sequences and are amenable to downstream sequencing or other analysis. Here, we report the development of a de novo molecular event recorder that processes information using a strand displacement reaction network and encodes the information using the primer exchange reaction, which can be decoded and quantified by DNA sequencing. The event recorder was able to classify the order at which different molecular signals appeared in time with 88% accuracy, the concentrations with 100% accuracy, and the duration with 75% accuracy. This simultaneous and highly programmable multiparameter recording could enable the large-scale deciphering of molecular events such as within dynamic reaction environments, living cells, or tissues.

     
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    Free, publicly-accessible full text available April 5, 2025