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.

合成信号受体可实现与定制输入耦合的可编程细胞反应。然而，设计一种力感应受体来重新连接机械传导仍然在很大程度上尚未被探索。在这里，我们引入了非基因工程人工机械感受器（AMR），能够重新编程非机械反应受体酪氨酸激酶（RTK）来感知用户定义的力线索，从而实现从头设计的机械转导。AMR 是一种模块化 DNA-蛋白质嵌合体，包含通过适体锚定物嫁接到天然 RTK 上的机械传感和传输 DNA 纳米装置。AMR 通过具有可调皮牛顿敏感力耐受力的变构 DNA 机械开关感知细胞间张力，启动力触发的动态 DNA 组装来操纵 RTK 二聚化并激活细胞内信号传导。通过交换力接收配体，我们证明了 AMR 介导的 c-Met（一种代表性 RTK）的激活，响应细胞粘附蛋白（整合素、E-钙粘蛋白）或膜蛋白内吞作用（CI）介导的细胞张力。 -M6PR）。此外，AMR还允许对另一种RTK FGFR1进行重编程，以定制机械生物学功能，例如粘附介导的神经干细胞维持。