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DNA-functionalized artificial mechanoreceptor for de novo force-responsive signaling.
Yang, Sihui; Wang, Miao; Tian, Dawei; Zhang, Xiaoyu; Cui, Kaiqing; Lü, Shouqin; Wang, Hong-Hui; Long, Mian; Nie, Zhou.
Afiliação
  • 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.
  • 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.
  • 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.
  • Zhang X; School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China.
  • Cui K; 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.
  • Lü S; School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China.
  • 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.
  • 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.
  • Nie Z; School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China.
Nat Chem Biol ; 20(8): 1066-1077, 2024 Aug.
Article em En | MEDLINE | ID: mdl-38448735
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA / Mecanotransdução Celular / Mecanorreceptores Limite: Humans Idioma: En Revista: Nat Chem Biol Assunto da revista: BIOLOGIA / QUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA / Mecanotransdução Celular / Mecanorreceptores Limite: Humans Idioma: En Revista: Nat Chem Biol Assunto da revista: BIOLOGIA / QUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China