Mechanically Triggered Hybridization Chain Reaction

• Type of Material: Article
• Authors: Yuxin Duan, Emory University; Roxanne Glazier, Georgia Institute of Technology; Alisina Bazrafshan, Emory University; Yuesong Hu, Emory University; Sk Aysha Rashid, Emory University; Brian Petrich, Emory University; Yonggang Ke, Emory University; Khalid Salaita, Emory University
• Language: English
• Date: 2021-07-29
• Publisher: WILEY-V C H VERLAG GMBH
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 Wiley‐VCH GmbH
• Final Published Version (URL): http://dx.doi.org/10.1002/anie.202107660
• Title of Journal or Parent Work: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• Volume: 60
• Issue: 36
• Start Page: 19974
• End Page: 19981
• Keywords: Chemistry; Science & Technology; PLATELET ACTIVATION; cellular receptor tension; drug screening; AMPLIFICATION; PROTEIN-KINASE; MOLECULAR TENSION; ADHESION; hybridization chain reaction; Physical Sciences; Chemistry, Multidisciplinary; nanotechnology; MECHANISMS; biosensors; FORCES

Abstract

Cells transmit piconewton forces to receptors to mediate processes such as migration and immune recognition. A major challenge in quantifying such forces is the sparsity of cell mechanical events. Accordingly, molecular tension is typically quantified with high resolution fluorescence microscopy, which hinders widespread adoption and application. Here, we report a mechanically triggered hybridization chain reaction (mechano-HCR) that allows chemical amplification of mechanical events. The amplification is triggered when a cell receptor mechanically denatures a duplex revealing a cryptic initiator to activate the HCR reaction in situ. Importantly, mechano-HCR enables direct readout of pN forces using a plate reader. We leverage this capability and measured mechano-IC50 for aspirin, Y-27632, and eptifibatide. Given that cell mechanical phenotypes are of clinical importance, mechano-HCR may offer a convenient route for drug discovery, personalized medicine, and disease diagnosis.