Synthetic transmembrane DNA receptors enable engineered sensing and actuation
Abstract In living organisms, cells synergistically couple cascade reaction pathways to achieve inter- and intracellular signal transduction by transmembrane protein receptors. The construction and assembly of synthetic receptor analogs that can mimic such biological processes is a central goal of s...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56758-1 |
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| _version_ | 1823861802252894208 |
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| author | Ze-Rui Zhou Man-Sha Wu Zhenglin Yang Yuting Wu Weijie Guo Da-Wei Li Ruo-Can Qian Yi Lu |
| author_facet | Ze-Rui Zhou Man-Sha Wu Zhenglin Yang Yuting Wu Weijie Guo Da-Wei Li Ruo-Can Qian Yi Lu |
| author_sort | Ze-Rui Zhou |
| collection | DOAJ |
| description | Abstract In living organisms, cells synergistically couple cascade reaction pathways to achieve inter- and intracellular signal transduction by transmembrane protein receptors. The construction and assembly of synthetic receptor analogs that can mimic such biological processes is a central goal of synthetic biochemistry and bionanotechnology to endow receptors with user-defined signal transduction effects. However, designing artificial transmembrane receptors with the desired input, output, and performance parameters are challenging. Here we show that the dimerization of synthetic transmembrane DNA receptors executes a systematically engineered sensing and actuation cascade in response to external molecular signals. The synthetic DNA receptors are composed of three parts, including an extracellular signal reception part, a lipophilic transmembrane anchoring part, and an intracellular signal output part. Upon the input of external signals, the DNA receptors can form dimers on the cell surface triggered by configuration changes, leading to a series of downstream cascade events including communication between donor and recipient cells, gene transcription regulation, protein level control, and cell apoptosis. We believe this work establishes a flexible cell surface engineering strategy that is broadly applicable to implement sophisticated biological functions. |
| format | Article |
| id | doaj-art-508274ade2ba481bbb761be30b498680 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-508274ade2ba481bbb761be30b4986802025-02-09T12:44:22ZengNature PortfolioNature Communications2041-17232025-02-0116111310.1038/s41467-025-56758-1Synthetic transmembrane DNA receptors enable engineered sensing and actuationZe-Rui Zhou0Man-Sha Wu1Zhenglin Yang2Yuting Wu3Weijie Guo4Da-Wei Li5Ruo-Can Qian6Yi Lu7Key Laboratory for Advanced Materials. East China University of Science and TechnologyKey Laboratory for Advanced Materials. East China University of Science and TechnologyDepartment of Chemistry, University of Texas at AustinDepartment of Chemistry, University of Texas at AustinDepartment of Molecular Biosciences, University of Texas at AustinKey Laboratory for Advanced Materials. East China University of Science and TechnologyKey Laboratory for Advanced Materials. East China University of Science and TechnologyDepartment of Chemistry, University of Texas at AustinAbstract In living organisms, cells synergistically couple cascade reaction pathways to achieve inter- and intracellular signal transduction by transmembrane protein receptors. The construction and assembly of synthetic receptor analogs that can mimic such biological processes is a central goal of synthetic biochemistry and bionanotechnology to endow receptors with user-defined signal transduction effects. However, designing artificial transmembrane receptors with the desired input, output, and performance parameters are challenging. Here we show that the dimerization of synthetic transmembrane DNA receptors executes a systematically engineered sensing and actuation cascade in response to external molecular signals. The synthetic DNA receptors are composed of three parts, including an extracellular signal reception part, a lipophilic transmembrane anchoring part, and an intracellular signal output part. Upon the input of external signals, the DNA receptors can form dimers on the cell surface triggered by configuration changes, leading to a series of downstream cascade events including communication between donor and recipient cells, gene transcription regulation, protein level control, and cell apoptosis. We believe this work establishes a flexible cell surface engineering strategy that is broadly applicable to implement sophisticated biological functions.https://doi.org/10.1038/s41467-025-56758-1 |
| spellingShingle | Ze-Rui Zhou Man-Sha Wu Zhenglin Yang Yuting Wu Weijie Guo Da-Wei Li Ruo-Can Qian Yi Lu Synthetic transmembrane DNA receptors enable engineered sensing and actuation Nature Communications |
| title | Synthetic transmembrane DNA receptors enable engineered sensing and actuation |
| title_full | Synthetic transmembrane DNA receptors enable engineered sensing and actuation |
| title_fullStr | Synthetic transmembrane DNA receptors enable engineered sensing and actuation |
| title_full_unstemmed | Synthetic transmembrane DNA receptors enable engineered sensing and actuation |
| title_short | Synthetic transmembrane DNA receptors enable engineered sensing and actuation |
| title_sort | synthetic transmembrane dna receptors enable engineered sensing and actuation |
| url | https://doi.org/10.1038/s41467-025-56758-1 |
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