Bioinspired Nucleic Acid-Based Bandpass Filters and Their Concentration-Adaptive Functions

Natural signaling networks can act as bandpass filters to interpret external stimuli within defined concentration ranges for differential cellular activities. Replicating such a bandpass filtering mechanism by synthetic networks poses a significant challenge. Herein, we introduce a modular design of nucleic acid-based multilayer threshold-gated incoherent feedforward networks as multiband bandpass filters to produce mutually exclusive responses within defined input concentration ranges. In these networks, nucleic acids demonstrate triple functionality by acting as threshold-gated entities to discern input concentration levels, serving as network nodes to assemble incoherent feedforward loops for nonlinear signal processing, and functioning as signal transduction units for coupling downstream functional modules. These modular networks enable the fine-tuning of filtering performance in terms of band position, bandwidth, cascades, and responses. A mathematical simulation model allows us to predict the filtering behaviors under various conditions. Also, the networks are integrated with upstream signal conversion modules to process concentration information on molecules beyond nucleic acids, such as adenosine and its derivatives. Furthermore, connections to downstream functional modules allow the system to regulate various processes in a concentration bandpass manner, realizing concentration-adaptive DNAzyme biocatalysis, tristate logic operations, RNA transcription, and DNA condensate formation. These findings underscore the potential of enzyme-free DNA reaction networks in complex signal processing and lay a solid foundation for developing chemical and material systems with highly adaptive and autonomous behaviors.