Mechanics play a fundamental role in cell biology, but detecting piconewton forces is challenging due to the lack of accessible and high throughput assays. Herein we report the mechanically-induced catalytic amplification reaction (MCR) for readout of receptor-mediated forces in cells. Mechanically labile DNA duplexes presenting ligands are surface immobilized such that specific receptor forces denature the duplex and thus expose a blocked primer. Amplification of primers is achieved using an isothermal polymerization reaction and quantified by fluorescence readout. As a proof-of-concept, the assay was used to test the activity of a mechano-modulatory drug and integrin adhesion receptor antibodies. To the best of our knowledge, this is the first example of a catalytic reaction triggered in response to molecular piconewton forces. The MCR may transform the field of mechanobiology by providing a new facile tool to detect receptor-specific mechanics with the convenience of the PCR.
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