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Mechanically Induced Catalytic Amplification Reaction for Readout of Receptor‐Mediated Cellular Forces
Author(s) -
Ma Victor PuiYan,
Liu Yang,
Yehl Kevin,
Galior Kornelia,
Zhang Yun,
Salaita Khalid
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201600351
Subject(s) - primer (cosmetics) , biophysics , mechanobiology , chemistry , receptor , rolling circle replication , molecular mechanics , integrin , catalysis , fluorescence , polymerization , nanotechnology , combinatorial chemistry , dna , polymerase , biochemistry , polymer , molecule , materials science , biology , microbiology and biotechnology , organic chemistry , physics , quantum mechanics
Mechanics play a fundamental role in cell biology, but detecting piconewton (pN) forces is challenging because of a lack of accessible and high throughput assays. A mechanically induced catalytic amplification reaction (MCR) for readout of receptor‐mediated forces in cells is described. 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 mechanomodulatory 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 polymerase chain reaction (PCR).