Volume 64, Issue 24 e202503903
Research Article

DNA-Based Signal Circuit for Self-Regulated Bidirectional Communication in Protocell-Living Cell Communities

Lexun Li

Lexun Li

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, FuRong Laboratory, College of Biology, Hunan University, Changsha, Hunan, 410082 China

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Shuang Liu

Shuang Liu

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, FuRong Laboratory, College of Biology, Hunan University, Changsha, Hunan, 410082 China

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Chundi Zhu

Chundi Zhu

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, FuRong Laboratory, College of Biology, Hunan University, Changsha, Hunan, 410082 China

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Shuxuan Shao

Shuxuan Shao

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, FuRong Laboratory, College of Biology, Hunan University, Changsha, Hunan, 410082 China

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Fan Yang

Fan Yang

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, FuRong Laboratory, College of Biology, Hunan University, Changsha, Hunan, 410082 China

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Qiaoling Liu

Corresponding Author

Qiaoling Liu

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, FuRong Laboratory, College of Biology, Hunan University, Changsha, Hunan, 410082 China

E-mail: [email protected]

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Weihong Tan

Weihong Tan

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, FuRong Laboratory, College of Biology, Hunan University, Changsha, Hunan, 410082 China

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Science, Hangzhou, Zhejiang, 310022 China

School of Materials Science and Engineering, Institute of Molecular Medicine (IMM), Renji Hospital Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240 China

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First published: 07 April 2025

Graphical Abstract

The intercellular communicating protocell with feedback loop was designed for self-regulating signal transmission in protocell/living cell community. This DNA-empowered protocell provides a bottom-up access route toward synthetic cellular systems with abilities for programming desired cellular behaviors.

Abstract

Developing synthetic biology tools to control cell-to-cell signaling can provide new capabilities to engineer cell-cell communication and program desired cellular behaviors. As cell mimics, abiotic protocells provide an attractive opportunity to modulate the intercellular communication with design-based regulatory features. Despite the chemical communication of protocells that interact with living cells have been demonstrated, the autonomous regulation of intercellular signal transmission in protocell/living cell community remains a critical challenge. Herein, we designed a DNA circuit consisting of a recognition module, activation module, and feedback module that enables protocells to self-regulate the interaction with living cells by sensing and responding to the signal released from living cells. The feedback module with renewable capability is capable of processing the signal transduction on the membrane surface of protocells and controlling intercellular adhesion. Once dissociated from living cells, the disengaged protocells allow the following interaction with multiple target living cells in succession. Overall, this work provides an avenue to control and program dynamic signal propagation in protocell/living cell community. The designed communication with living cells would open new ways to tune cellular behavior and apply them to cell-based therapeutics.

Conflict of Interests

The authors declare no conflict of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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