Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 55, Issue 18, Pages 5488-5492Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201600351
Keywords
drug screening; integrins; mechanically induced catalytic amplification; receptor-mediated forces; rolling circle amplification
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Funding
- NIH [R01-GM097399]
- Alfred P. Sloan Research Fellowship
- Camille-Dreyfus Teacher-Scholar Award
- NSF CAREER Award [1350829]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1350829] Funding Source: National Science Foundation
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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).
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