High-throughput screening for modulators of cellular contractile force

Chan Young Park, Enhua H. Zhou, Dhananjay Tambe, Bohao Chen, Tera Lavoie, Maria Dowell, Anton Simeonov, David J. Maloney, Aleksandar Marinkovic, Daniel J. Tschumperlin, Stephanie Burger, Matthew Frykenberg, James P. Butler, W. Daniel Stamer, Mark Johnson, Julian Solway, Jeffrey J. Fredberg, Ramaswamy Krishnan

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

When cellular contractile forces are central to pathophysiology, these forces comprise a logical target of therapy. Nevertheless, existing high-throughput screens are limited to upstream signalling intermediates with poorly defined relationships to such a physiological endpoint. Using cellular force as the target, here we report a new screening technology and demonstrate its applications using human airway smooth muscle cells in the context of asthma and Schlemm's canal endothelial cells in the context of glaucoma. This approach identified several drug candidates for both asthma and glaucoma. We attained rates of 1000 compounds per screening day, thus establishing a force-based cellular platform for high-throughput drug discovery.

Original languageEnglish (US)
Pages (from-to)1318-1324
Number of pages7
JournalIntegrative Biology (United Kingdom)
Volume7
Issue number10
DOIs
StatePublished - Oct 1 2015

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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    Park, C. Y., Zhou, E. H., Tambe, D., Chen, B., Lavoie, T., Dowell, M., Simeonov, A., Maloney, D. J., Marinkovic, A., Tschumperlin, D. J., Burger, S., Frykenberg, M., Butler, J. P., Stamer, W. D., Johnson, M., Solway, J., Fredberg, J. J., & Krishnan, R. (2015). High-throughput screening for modulators of cellular contractile force. Integrative Biology (United Kingdom), 7(10), 1318-1324. https://doi.org/10.1039/c5ib00054h