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DNA-functionalized artificial mechanoreceptor for de novo force-responsive signaling
Yang, Sihui; Wang, Miao; Tian DW(田大伟); Zhang XY(张晓宇); Cui, Kaiqing; Lv SQ(吕守芹); Wang, Honghui; Long M(龙勉); Nie, Zhou
Source PublicationNATURE CHEMICAL BIOLOGY
2024-08
Volume20Issue:8Pages:260-271
ISSN1552-4450
AbstractSynthetic 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. Yang et al. reported the development of nongenetically engineered artificial mechanoreceptors capable of reprogramming non-mechanoresponsive receptors to sense user-defined force cues, enabling de novo-designed mechanotransduction.
DOI10.1038/s41589-024-01572-x
Indexed BySCI
Language英语
WOS IDWOS:001179723500002
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
Funding OrganizationNational Natural Science Foundation of China (National Science Foundation of China) {2020YFA0907500, 2021YFA0910100] ; National Key Research and Development Program of China {22034002, 92253304, 22177030] ; National Natural Science Foundation of China
Classification一类
Ranking1
ContributorNie Z
Citation statistics
Document Type期刊论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/97233
Collection微重力重点实验室
Affiliation1.【Yang, Sihui & Wang, Miao & Cui, Kaiqing & Wang, Hong-hui & Nie, Zhou】 Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Hunan Prov Key Lab Biomacromol Chem Biol,Coll Biol, Changsha, Peoples R China
2.【Tian, Dawei & Zhang, Xiaoyu & Lu, Shouqin & Long, Mian】 Chinese Acad Sci, Beijing Key Lab Engn Construct & Mechanobiol, Ctr Biomech & Bioengn, Key Lab Micrograv,Natl Micrograv Lab,Inst Mech, Beijing, Peoples R China
3.【Tian, Dawei & Zhang, Xiaoyu & Lu, Shouqin & Long, Mian】 Univ Chinese Acad Sci, Sch Engn Sci, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Yang, Sihui,Wang, Miao,Tian DW,et al. DNA-functionalized artificial mechanoreceptor for de novo force-responsive signaling[J]. NATURE CHEMICAL BIOLOGY,2024,20,8,:260-271.Rp_Au:Nie Z
APA Yang, Sihui.,Wang, Miao.,田大伟.,张晓宇.,Cui, Kaiqing.,...&Nie, Zhou.(2024).DNA-functionalized artificial mechanoreceptor for de novo force-responsive signaling.NATURE CHEMICAL BIOLOGY,20(8),260-271.
MLA Yang, Sihui,et al."DNA-functionalized artificial mechanoreceptor for de novo force-responsive signaling".NATURE CHEMICAL BIOLOGY 20.8(2024):260-271.
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