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

doi:10.1039/c5ib00054h

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

Physiology & Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

37 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 language	English (US)
Pages (from-to)	1318-1324
Number of pages	7
Journal	Integrative Biology (United Kingdom)
Volume	7
Issue number	10
DOIs	https://doi.org/10.1039/c5ib00054h
State	Published - Oct 1 2015

ASJC Scopus subject areas

General Medicine

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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

Park, CY, Zhou, EH, Tambe, D, Chen, B, Lavoie, T, Dowell, M, Simeonov, A, Maloney, DJ, Marinkovic, A, Tschumperlin, DJ, Burger, S, Frykenberg, M, Butler, JP, Stamer, WD, Johnson, M, Solway, J, Fredberg, JJ & Krishnan, R 2015, 'High-throughput screening for modulators of cellular contractile force', Integrative Biology (United Kingdom), vol. 7, no. 10, pp. 1318-1324. https://doi.org/10.1039/c5ib00054h

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High-throughput screening for modulators of cellular contractile force

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