Synthetic Genetic Reversible Feynman Gate in a Single E. coli Cell and Its Application in Bacterial to Mammalian Cell Information Transfer

Abstract

Reversible computing is a nonconventional form of computing where the inputs and outputs are mapped in a unique one-to-one fashion. Reversible logic gates in single living cells have not been demonstrated. Here, we constructed a synthetic genetic reversible Feynman gate in single E. coli cells, and the input− output relations were measured in a clonal population. The inputs were extracellular chemicals, isopropyl β-D-1-thiogalactopyranoside (IPTG), and anhydrotetracycline (aTc), and the outputs were two fluorescence proteins. We developed a simple mathematical model and simulation to capture the essential features of the circuit and experimentally demonstrated that the behavior of the circuit was ultrasensitive and predictive. We showed an application by creating an intercellular Feynman gate, where input information from bacteria was computed and transferred to HeLa cells through shRNAs delivery and the output signals were observed as silencing of native AKT1 and CTNNB1 genes. The introduction of reversible logics in synthetic biology is new, and given that one-to-one input−output mapping, such reversible genetic systems might have applications in sensing, diagnostics, cellular computing, and synthetic biology.

A Logically Reversible Double Feynman Gate with Molecular Engineered Bacteria Arranged in an Artificial Neural Network-Type Architecture

“…However, not many reversible logic gates have been built into living cells. We have previously reported a 2-bit Feynman gate in bacterial and mammalian cells and a 3-bit Fredkin gate in bacterial cells. , The successful implementation of the 3-bit double Feynman gate in this study expands the scope of reversible logic devices in synthetic biology.…”

“…We have previously reported a 2-bit Feynman gate in bacterial and mammalian cells and a 3-bit Fredkin gate in bacterial cells. 17,18 The successful implementation of the 3-bit double Feynman gate in this study expands the scope of reversible logic devices in synthetic biology. In summary, we constructed a 3-input−3-output synthetic genetic reversible double Feynman logic gate with molecular engineered E. coli cells, based on a single-layer artificial network architecture.…”

“…Logical reversibility has been demonstrated in vitro biochemical reactions, where the logical reversibility but not the thermodynamic reversibility of Fredkin and Toffoli has been implemented using in vitro DNA computation and enzyme catalyzed reactions . We recently demonstrated logical reversibility in living cells by implementing Feynman and Fredkin gates using synthetic genetic circuits in E. coli and human cells. , In living biological cells, which follow the principle of nonequilibrium thermodynamics, attaining true thermodynamic reversibility is impossible. Yet, from a computing perspective, living cells would be an attractive platform for reversible computing due to the efficient energy budget of biological reactions.…”

“…16 We recently demonstrated logical reversibility in living cells by implementing Feynman and Fredkin gates using synthetic genetic circuits in E. coli and human cells. 17,18 In living biological cells, which follow the principle of nonequilibrium thermodynamics, attaining true thermodynamic reversibility is impossible. Yet, from a computing perspective, living cells would be an attractive platform for reversible computing due to the efficient energy budget of biological reactions.…”