High-throughput screening for modulators of cellular contractile force.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • October 2015

Published In

Volume / Issue

  • 7 / 10

Start / End Page

  • 1318 - 1324

PubMed ID

  • 25953078

Pubmed Central ID

  • PMC4657543

Electronic International Standard Serial Number (EISSN)

  • 1757-9708

Digital Object Identifier (DOI)

  • 10.1039/c5ib00054h

Language

  • eng

Conference Location

  • England