DNA-functionalized artificial mechanoreceptor for de novo force-responsive signaling
Sihui Yang1, Miao Wang1, Dawei Tian2,3
1State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, China.
Nature Chemical Biology
|March 6, 2024
Summary
Researchers engineered artificial mechanoreceptors (AMRs) to reprogram cells, enabling them to sense and respond to specific forces. This breakthrough allows for custom control over cellular signaling pathways by rewiring mechanotransduction.
Area of Science:
- Biotechnology
- Molecular Biology
- Cellular Mechanobiology
Background:
- Synthetic signaling receptors offer programmable cellular responses.
- Engineering force-sensing receptors to control mechanotransduction is an underexplored area.
Purpose of the Study:
- To introduce nongenetically engineered artificial mechanoreceptors (AMRs) for reprogramming non-mechanoresponsive receptor tyrosine kinases (RTKs).
- To enable de novo-designed mechanotransduction by sensing user-defined force cues.
Main Methods:
- AMRs are modular DNA-protein chimeras with a DNA nanodevice and aptameric anchors on RTKs.
- An allosteric DNA mechano-switch senses intercellular tensile force (piconewton range).
- Force-triggered DNA assembly manipulates RTK dimerization and activates intracellular signaling.
Main Results:
- AMRs reprogrammed c-Met (a RTK) to sense forces from cell-adhesion proteins and endocytosis.
- AMRs enabled reprogramming of FGFR1 (another RTK) for customized mechanobiological functions.
- Demonstrated adhesion-mediated neural stem cell maintenance using AMR-FGFR1.
Conclusions:
- AMRs provide a novel platform for engineering de novo mechanotransduction.
- This technology allows for precise control over cellular responses to mechanical stimuli.
- AMRs have potential applications in customizing cell behavior for research and therapeutics.
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