Oriented triplex DNA as a synthetic receptor for transmembrane signal transduction

Hui Chen, Shaohong Zhou, Kleins Ngocho, Jing Zheng, Xiaoxiao He, Jin Huang, Kemin Wang, Hui Shi and Jianbo Liu ()
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Hui Chen: Hunan University
Shaohong Zhou: Hunan University
Kleins Ngocho: Hunan University
Jing Zheng: Hunan University
Xiaoxiao He: Hunan University
Jin Huang: Hunan University
Kemin Wang: Hunan University
Hui Shi: Hunan University
Jianbo Liu: Hunan University

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Signal transduction across biological membranes enables cells to detect and respond to diverse chemical or physical signals, and replicating these complex biological processes through synthetic methods is of significant interest in synthetic biology. Here we present an artificial signal transduction system using oriented cholesterol-tagged triplex DNA (TD) as synthetic receptors to transmit and amplify signals across lipid bilayer membranes through H+-mediated TD conformational transitions from duplex to triplex. An auxiliary sequence, complementary to the third strand of the TD, ensures a controlled and preferred outward orientation of cholesterol-tagged TD on membranes. Upon external H+ stimuli, the conformational change triggers the translocation of the third strand from the outer to the inner membrane leaflet, resulting in effective transmembrane signal transduction. This mechanism enables fluorescence resonance energy transfer (FRET), selective photocleavage, catalytic signal amplification, and logic gate modulation within vesicles. Our findings demonstrate that these TD-based receptors mimic the functional dynamics of natural G protein-coupled receptors (GPCRs), providing a foundation for advanced applications in biosensing, cell signaling modulation, and targeted drug delivery systems.

Date: 2024
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DOI: 10.1038/s41467-024-53960-5

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