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

arXiv · 1411.5695

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

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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 signaling intermediates with poorly defined relationship to such a physiological endpoint. Using cellular force as the target, here we screened libraries to identify novel drug candidates in the case of human airway smooth muscle cells in the context of asthma, and also in the case of 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.

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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. 2014-11-20. High-throughput screening for modulators of cellular contractile force. https://arxiv.org/abs/1411.5695

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