DNA-functionalized artificial mechanoreceptor for de novo force-responsive signaling.

Journal

Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976

Informations de publication

Date de publication:
06 Mar 2024
Historique:
received: 15 02 2023
accepted: 07 02 2024
medline: 7 3 2024
pubmed: 7 3 2024
entrez: 6 3 2024
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1038/s41589-024-01572-x PMID: 38448735
pubmed: 38448735
doi: 10.1038/s41589-024-01572-x
pii: 10.1038/s41589-024-01572-x
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 22034002
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 92253304
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 22177030

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Sihui Yang (S)

State 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.

Miao Wang (M)

State 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.

Dawei Tian (D)

Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China.

Xiaoyu Zhang (X)

Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China.

Kaiqing Cui (K)

State 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.

Shouqin Lü (S)

Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China.
ORCID: 0000-0003-0830-9507

Hong-Hui Wang (HH)

State 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.
ORCID: 0000-0002-4420-9733

Mian Long (M)

Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China.
ORCID: 0000-0003-0819-6186

Zhou Nie (Z)

State 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. niezhou.hnu@gmail.com.
ORCID: 0000-0001-9864-2965

Classifications MeSH