Design of a Biohybrid Materials Circuit with Binary Decoder Functionality

Synthetic biology applies concepts from electrical engineering and information processing to endow cells with computational functionality. Transferring the underlying molecular components into materials and wiring them according to topologies inspired by electronic circuit boards has yielded materials systems that perform selected computational operations. However, the limited functionality of available building blocks is restricting the implementation of advanced information-processing circuits into materials. Here, a set of protease-based biohybrid modules the bioactivity of which can either be induced or inhibited is engineered. Guided by a quantitative mathematical model and following a design-build-test-learn (DBTL) cycle, the modules are wired according to circuit topologies inspired by electronic signal decoders, a fundamental motif in information processing. A 2-input/4-output binary decoder for the detection of two small molecules in a material framework that can perform regulated outputs in form of distinct protease activities is designed. The here demonstrated smart material system is strongly modular and can be used for biomolecular information processing for example in advanced biosensing or drug delivery applications. Biohybrid materials that communicate with each other via diffusible inhibitory or activating signals are assembled in a circuit topology inspired by an electronical binary 2-input/4-output decoder. The decoder is programmed to convert different combinations of two input signals into the release of distinct protease outputs. Such information-processing biohybrid material circuits can be used for biomolecular computing and signal processing.image