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.

Replicating signal transduction seen in cells is of interest in synthetic biology. Here, the authors report on an artificial membrane receptor based on the conformational changes of triplex DNA designed to mimic G-protein coupled receptors for transmembrane signal transduction and amplification without physical mass exchange.

Details

Title
Oriented triplex DNA as a synthetic receptor for transmembrane signal transduction
Author
Chen, Hui 1 ; Zhou, Shaohong 1 ; Ngocho, Kleins 1 ; Zheng, Jing 1 ; He, Xiaoxiao 1 ; Huang, Jin 1   VIAFID ORCID Logo  ; Wang, Kemin 1   VIAFID ORCID Logo  ; Shi, Hui 1 ; Liu, Jianbo 1   VIAFID ORCID Logo 

 Hunan University, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Changsha, People’s Republic of China (GRID:grid.67293.39) 
Pages
9789
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3127428821
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.