High-throughput screening for modulators of cellular contractile force.
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.
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
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