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 Publication | NATURE CHEMICAL BIOLOGY |
2024-08 | |
Volume | 20Issue:8Pages:260-271 |
ISSN | 1552-4450 |
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. 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. |
DOI | 10.1038/s41589-024-01572-x |
Indexed By | SCI |
Language | 英语 |
WOS ID | WOS:001179723500002 |
WOS Research Area | Biochemistry & Molecular Biology |
WOS Subject | Biochemistry & Molecular Biology |
Funding Organization | National 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 |
Ranking | 1 |
Contributor | Nie Z |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://dspace.imech.ac.cn/handle/311007/97233 |
Collection | 微重力重点实验室 |
Affiliation | 1.【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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