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Author Notes:

Corresponding Author: Dr. Khalid Salaita E-mail address: k.salaita@emory.edu Department of Chemistry, Emory University, Atlanta, GA, USA.

Subjects:

Research Funding:

K.S. would like to thank for the financial support from the NIH (R01-GM097399), the Alfred P. Sloan Research Fellowship, the Camille-Dreyfus Teacher-Scholar Award, and the NSF CAREER Award (1350829).

Keywords:

  • Science & Technology
  • Physical Sciences
  • Chemistry, Multidisciplinary
  • Chemistry
  • drug screening
  • integrins
  • mechanically induced catalytic amplification
  • receptor-mediated forces
  • rolling circle amplification
  • FOCAL ADHESIONS
  • INTEGRIN FORCES
  • DNA-POLYMERASE
  • TENSION
  • MECHANOTRANSDUCTION
  • PROBES
  • MOLECULES
  • SURFACE
  • CELLS

Mechanically Induced Catalytic Amplification Reaction for Readout of Receptor-Mediated Cellular Forces

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Journal Title:

Angewandte Chemie International Edition

Volume:

Volume 55, Number 18

Publisher:

, Pages 5488-5492

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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).

Copyright information:

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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