Phase Separation of DNA-Encoded Artificial Cells Boosts Signal Amplification for Biosensing

Juncai Li; Cai Yang; Lizhuan Zhang; Chunying Li; Sitao Xie; Ting Fu; Ziwen Zhang; Longjie Li; Lubin Qi; Yifan Lyu; Fengming Chen; Lei He; Weihong Tan

doi:10.1002/anie.202306691

Phase Separation of DNA-Encoded Artificial Cells Boosts Signal Amplification for Biosensing

Angew Chem Int Ed Engl. 2023 Sep 25;62(39):e202306691. doi: 10.1002/anie.202306691. Epub 2023 Aug 17.

Authors

Juncai Li^{1

2}, Cai Yang^{1

3}, Lizhuan Zhang¹, Chunying Li¹, Sitao Xie¹, Ting Fu^{1

3}, Ziwen Zhang¹, Longjie Li¹, Lubin Qi^{1

2}, Yifan Lyu³, Fengming Chen³, Lei He¹, Weihong Tan^{1

3

4}

Affiliations

¹ The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
² Institute of Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, 100190, China.
³ Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.
⁴ Institute of Molecular Medicine (IMM), Renji Hospital, Shanghai Jiao Tong University School of Medicine, College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

PMID: 37455257
DOI: 10.1002/anie.202306691

Abstract

Life-like hierarchical architecture shows great potential for advancing intelligent biosensing, but modular expansion of its sensitivity and functionality remains a challenge. Drawing inspiration from intracellular liquid-liquid phase separation, we discovered that a DNA-encoded artificial cell with a liquid core (LAC) can enhance peroxidase-like activity of Hemin and its DNA G-quadruplex aptamer complex (DGAH) without substrate-selectivity, unlike its gelled core (GAC) counterpart. The LAC is easily engineered as an ultrasensitive biosensing system, benefiting from DNA's high programmability and unique signal amplification capability mediated by liquid-liquid phase separation. As proof of concept, its versatility was successfully demonstrated by coupling with two molecular recognition elements to monitor tumor-related microRNA and profile cancer cell phenotypes. This scalable design philosophy offers new insights into the design of next generation of artificial cells-based biosensors.

Keywords: Aptamers; Artificial Cell; Biosensing; Liquid-Liquid Separation; Signal Amplification.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aptamers, Nucleotide*
Artificial Cells*
Biosensing Techniques*
DNA / genetics
DNA, Catalytic* / metabolism
G-Quadruplexes*
Hemin
Humans
MicroRNAs*
Neoplasms*

Substances

DNA
MicroRNAs
Hemin
DNA, Catalytic
Aptamers, Nucleotide