title: High-throughput screening for modulators of cellular contractile force.
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.
authors.affiliation: Molecular and Integrative Physiological Sciences, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Park
authors.forename: Enhua H
authors.initials: EH
authors.lastname: Zhou
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Tambe
authors.forename: Bohao
authors.initials: B
authors.lastname: Chen
authors.forename: Tera
authors.initials: T
authors.lastname: Lavoie
authors.forename: Maria
authors.initials: M
authors.lastname: Dowell
authors.forename: Anton
authors.initials: A
authors.lastname: Simeonov
authors.forename: David J
authors.initials: DJ
authors.lastname: Maloney
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Marinkovic
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Tschumperlin
authors.forename: Stephanie
authors.initials: S
authors.lastname: Burger
authors.forename: Matthew
authors.initials: M
authors.lastname: Frykenberg
authors.forename: James P
authors.initials: JP
authors.lastname: Butler
authors.forename: W Daniel
authors.initials: WD
authors.lastname: Stamer
authors.forename: Mark
authors.initials: M
authors.lastname: Johnson
authors.forename: Julian
authors.initials: J
authors.lastname: Solway
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fredberg
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Krishnan
mesh_terms: D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology*; D005583:Fourier Analysis; D005901:Glaucoma / Q000188:drug therapy / Q000503:physiopathology; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology*