1. DNA-functionalized artificial mechanoreceptor for de novo force-responsive signaling.
- Author
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Yang S, Wang M, Tian D, Zhang X, Cui K, Lü S, Wang HH, Long M, and Nie Z
- Subjects
- Humans, Signal Transduction drug effects, Receptor, Fibroblast Growth Factor, Type 1 metabolism, Proto-Oncogene Proteins c-met metabolism, Receptor Protein-Tyrosine Kinases metabolism, Cadherins metabolism, Cadherins genetics, DNA metabolism, DNA chemistry, Mechanotransduction, Cellular drug effects, Mechanoreceptors metabolism
- Abstract
Synthetic signaling receptors enable programmable cellular responses coupling with customized inputs. However, engineering a designer force-sensing receptor to rewire mechanotransduction remains largely unexplored. Herein, we introduce nongenetically engineered artificial mechanoreceptors (AMRs) capable of reprogramming non-mechanoresponsive receptor tyrosine kinases (RTKs) to sense user-defined force cues, enabling de novo-designed mechanotransduction. AMR is a modular DNA-protein chimera comprising a mechanosensing-and-transmitting DNA nanodevice grafted on natural RTKs via aptameric anchors. AMR senses intercellular tensile force via an allosteric DNA mechano-switch with tunable piconewton-sensitive force tolerance, actuating a force-triggered dynamic DNA assembly to manipulate RTK dimerization and activate intracellular signaling. By swapping the force-reception ligands, we demonstrate the AMR-mediated activation of c-Met, a representative RTK, in response to the cellular tensile forces mediated by cell-adhesion proteins (integrin, E-cadherin) or membrane protein endocytosis (CI-M6PR). Moreover, AMR also allows the reprogramming of FGFR1, another RTK, to customize mechanobiological function, for example, adhesion-mediated neural stem cell maintenance., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2024
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