A DNA-functionalized artificial chimeric mechanoreceptor (AMR) is introduced for de novo force-responsive cellular signaling. AMR is a modular DNA-protein chimera that enables non-mechanoresponsive receptor tyrosine kinases (RTKs) to sense user-defined force cues, facilitating de novo mechanotransduction. The AMR consists of a mechanosensing-and-transmitting DNA nanodevice grafted onto natural RTKs via aptameric anchors. The DNA nanodevice contains an allosteric DNA mechano-switch that senses intercellular tensile force and triggers a force-triggered dynamic DNA assembly to manipulate RTK dimerization and activate intracellular signaling. By swapping the force-reception ligands, the AMR can activate c-Met, a representative RTK, in response to cellular tensile forces mediated by cell-adhesion proteins or membrane protein endocytosis. The versatility of AMR allows the reprogramming of FGFR1 to customize mechanobiological functions, such as adhesion-mediated neural stem cell maintenance. The DNA-functionalized AMR presents an alternative mechanotransduction machinery independent of natural protein-based mechano-switches. The AMR's ability to nongenetically repurpose non-mechanoresponsive receptor signaling offers a promising synthetic toolkit for mechanobiological research and biomedical applications. The AMR platform is highly modular, allowing for the customization of force input-output programs by plugging in diverse cognate ligands. The AMR can sense and transmit external tractile forces via a force-triggered toehold-mediated strand displacement reaction (F-TSDR). The AMR's force sensitivity can be tuned by adjusting the GC content, stem length, and loop size of the DNA hairpin. The AMR can be tailored to respond to various cell-generated mechanical forces, including those mediated by adhesion proteins or membrane protein endocytosis. The AMR can also be used to reprogram mechanobiological functions, such as adhesion-mediated neural stem cell maintenance. The AMR platform enables the de novo design of mechanotransduction, allowing for the reprogramming of cellular signaling in response to mechanical cues. The AMR strategy provides a valuable toolkit for understanding mechanobiology and developing force-responsive cell-based therapies in regenerative medicine.A DNA-functionalized artificial chimeric mechanoreceptor (AMR) is introduced for de novo force-responsive cellular signaling. AMR is a modular DNA-protein chimera that enables non-mechanoresponsive receptor tyrosine kinases (RTKs) to sense user-defined force cues, facilitating de novo mechanotransduction. The AMR consists of a mechanosensing-and-transmitting DNA nanodevice grafted onto natural RTKs via aptameric anchors. The DNA nanodevice contains an allosteric DNA mechano-switch that senses intercellular tensile force and triggers a force-triggered dynamic DNA assembly to manipulate RTK dimerization and activate intracellular signaling. By swapping the force-reception ligands, the AMR can activate c-Met, a representative RTK, in response to cellular tensile forces mediated by cell-adhesion proteins or membrane protein endocytosis. The versatility of AMR allows the reprogramming of FGFR1 to customize mechanobiological functions, such as adhesion-mediated neural stem cell maintenance. The DNA-functionalized AMR presents an alternative mechanotransduction machinery independent of natural protein-based mechano-switches. The AMR's ability to nongenetically repurpose non-mechanoresponsive receptor signaling offers a promising synthetic toolkit for mechanobiological research and biomedical applications. The AMR platform is highly modular, allowing for the customization of force input-output programs by plugging in diverse cognate ligands. The AMR can sense and transmit external tractile forces via a force-triggered toehold-mediated strand displacement reaction (F-TSDR). The AMR's force sensitivity can be tuned by adjusting the GC content, stem length, and loop size of the DNA hairpin. The AMR can be tailored to respond to various cell-generated mechanical forces, including those mediated by adhesion proteins or membrane protein endocytosis. The AMR can also be used to reprogram mechanobiological functions, such as adhesion-mediated neural stem cell maintenance. The AMR platform enables the de novo design of mechanotransduction, allowing for the reprogramming of cellular signaling in response to mechanical cues. The AMR strategy provides a valuable toolkit for understanding mechanobiology and developing force-responsive cell-based therapies in regenerative medicine.