Synthetic mechanoreceptor engineering: From genetic encoding to DNA nanotechnology-based reprogramming

Precise modulation of mechanoreceptor-mediated signal transduction is crucial for decoding cellular mechanotransduction mechanisms and programming cell fate. This review provides a comprehensive summary of recent advances in engineering synthetic mechanoreceptors, spanning from protein-centric genetic encoding to DNA nanotechnology-based non-genetic reprogramming strategies. Genetic engineering strategies employ protein structure encoding and site-directed mutagenesis to reprogram force-response functions in natural mechanoreceptors. As a complementary non-genetic approach, DNA nanotechnology leverages its programmability, modularity, and predictable mechanical properties to achieve precise control over receptor functionalities. The flourishing development of DNA mechanosensitive nanodevices has provided a promising synthetic toolkit for manipulating mechanoreceptors, enabling precise control over receptor spatial organization and signal transduction. A key innovation is the development of novel DNA-functionalized artificial mechanoreceptors (AMRs), which confer force-responsiveness to naturally non-mechanosensitive receptors without genetic modification, thereby enabling customized mechanotransduction and mechanobiological applications. Collectively, this paradigm shift highlights DNA-based non-genetic receptor engineering as a versatile and powerful toolkit, paving new avenues for mechanobiology research and pioneering force-directed therapeutic strategies in regenerative medicine.