Abstract

Feedforward and feedback loops are key regulatory elements in cellular signaling and information processing. Synthetic biology exploits these elements for the design of molecular circuits that enable the reprogramming and control of specific cellular functions. These circuits serve as a basis for the engineering of complex cellular networks, opening the door for numerous medical and biotechnological applications. Here, a similar principle is applied. Feedforward and positive feedback circuits are incorporated into biohybrid polymer materials in order to develop signal‐sensing and signal‐processing devices. This concept is exemplified by the detection of the proteolytic activity of the botulinum neurotoxin A. To this aim, site‐specific proteases are incorporated into receiver, transmitter, and output materials, and their release, diffusion, and/or activation are wired according to a feedforward or a positive feedback circuit. The development of a quantitative mathematical model enables analysis and comparison of the performance of both systems. The flexible design could be easily adapted to detect other toxins or molecules of interest. Furthermore, cellular signaling or gene regulatory pathways could provide additional blueprints for the development of novel biohybrid circuits. Such information‐processing, material‐embedded biological circuits hold great promise for a variety of analytical, medical, or biotechnological applications.

Highlights

  • Most signaling pathways are characterized by complex feedforward porated into receiver, transmitter, and output materials, and their release, and feedback regulation and crosstalk diffusion, and/or activation are wired according to a feedforward or a positive feedback circuit

  • To develop polymer material-embedded circuits for the sensing and processing of input signals, we evaluated two design motifs inspired by information-processing circuits in cellular signal transduction[1,23,24] and synthetic biology:[25] one design was based on a positive feedforward loop (Figure 1A,B) the other on a positive feedback loop (Figure 1C,D)

  • We incorporated the enzymatic cascades into polymer materials by designing four modules interconnected in a positive feedforward loop (Figure 1B) or in a positive feedback loop (Figure 1D) configuration

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Summary

Introduction

In order to react to changes in their environment, living organisms must perceive and process specific signals. Feedforward and positive feedback circuits are incorporated into biohybrid polymer materials in order to develop signal-sensing and signal-processing devices This concept is exemplified by the detection of the proteolytic activity of the botulinum neurotoxin A. The field of synthetic biology has harnessed the deepened understanding of signaling pathways and networks to design and engineer novel, synthetic signprovide additional blueprints for the development of novel biohybrid circuits. Such information-processing, material-embedded biological circuits hold great promise for a variety of analytical, medical, or biotechnological applications

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