Literature DB >> 29266960

FLECS Technology for High-Throughput Single-Cell Force Biology and Screening.

Ivan Pushkarsky1,2.   

Abstract

Dr. Ivan Pushkarsky from the Department of Bioengineering at UCLA and Forcyte Biotechnologies, Inc. was awarded The President's Innovation Award at the Annual Society of Biomolecular Imaging and Informatics meeting held in San Diego, September 2017. All cell types produce mechanical forces to serve important physiological roles. Since aberrant force-generating phenotypes directly lead to disease, cellular force-generation mechanisms are high-value targets for new therapies. Despite knowledge of their significance in disease, drug developers have had limited access to force-generating cellular phenotypes, especially in the context of high-throughput screening. To serve this valuable need, we have developed a platform microtechnology called "FLECS" that can acquire robust contractility data from 1000s of uniformly patterned single cells simultaneously and seamlessly integrates with the 96- and 384-well plate formats to facilitate large-scale drug screens. This perspective discusses the challenges facing existing laboratory methods for measuring cellular force in the context of drug discovery. It then provides an overview of the FLECS platform, describes how it was designed to overcome many of these challenges, and discusses some exciting work already accomplished with FLECS. It concludes by highlighting the platform nature of the technology and the potential value that it promises for a myriad of drug development efforts.

Keywords:  asthma; cellular force; contractility; force generation; hypertension; smooth muscle cells

Mesh:

Year:  2017        PMID: 29266960      PMCID: PMC5775112          DOI: 10.1089/adt.2017.825

Source DB:  PubMed          Journal:  Assay Drug Dev Technol        ISSN: 1540-658X            Impact factor:   1.738


  18 in total

1.  Cells lying on a bed of microneedles: an approach to isolate mechanical force.

Authors:  John L Tan; Joe Tien; Dana M Pirone; Darren S Gray; Kiran Bhadriraju; Christopher S Chen
Journal:  Proc Natl Acad Sci U S A       Date:  2003-01-27       Impact factor: 11.205

Review 2.  Tissue cells feel and respond to the stiffness of their substrate.

Authors:  Dennis E Discher; Paul Janmey; Yu-Li Wang
Journal:  Science       Date:  2005-11-18       Impact factor: 47.728

Review 3.  Molecular mechanisms underlying airway smooth muscle contraction and proliferation: implications for asthma.

Authors:  Girolamo Pelaia; Teresa Renda; Luca Gallelli; Alessandro Vatrella; Maria Teresa Busceti; Sergio Agati; Mario Caputi; Mario Cazzola; Rosario Maselli; Serafino A Marsico
Journal:  Respir Med       Date:  2008-06-24       Impact factor: 3.415

4.  Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery.

Authors:  Muge Yemisci; Yasemin Gursoy-Ozdemir; Atay Vural; Alp Can; Kamil Topalkara; Turgay Dalkara
Journal:  Nat Med       Date:  2009-08-30       Impact factor: 53.440

5.  Relaxin regulates myofibroblast contractility and protects against lung fibrosis.

Authors:  Xiangwei Huang; Ying Gai; Naiheng Yang; Baogen Lu; Chrishan S Samuel; Victor J Thannickal; Yong Zhou
Journal:  Am J Pathol       Date:  2011-10-06       Impact factor: 4.307

6.  ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma.

Authors:  Victoria Sanz-Moreno; Cedric Gaggioli; Maggie Yeo; Jean Albrengues; Fredrik Wallberg; Amaya Viros; Steven Hooper; Richard Mitter; Chloé C Féral; Martin Cook; James Larkin; Richard Marais; Guerrino Meneguzzi; Erik Sahai; Chris J Marshall
Journal:  Cancer Cell       Date:  2011-08-16       Impact factor: 31.743

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

Authors:  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
Journal:  Integr Biol (Camb)       Date:  2015-05-08       Impact factor: 2.192

8.  Synchrony of cell spreading and contraction force as phagocytes engulf large pathogens.

Authors:  E Evans; A Leung; D Zhelev
Journal:  J Cell Biol       Date:  1993-09       Impact factor: 10.539

9.  Cytoskeletal forces during signaling activation in Jurkat T-cells.

Authors:  King Lam Hui; Lakshmi Balagopalan; Lawrence E Samelson; Arpita Upadhyaya
Journal:  Mol Biol Cell       Date:  2014-12-17       Impact factor: 4.138

10.  Force transmission in migrating cells.

Authors:  Maxime F Fournier; Roger Sauser; Davide Ambrosi; Jean-Jacques Meister; Alexander B Verkhovsky
Journal:  J Cell Biol       Date:  2010-01-25       Impact factor: 10.539

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  1 in total

1.  Obesity increases airway smooth muscle responses to contractile agonists.

Authors:  Sarah Orfanos; Joseph Jude; Brian T Deeney; Gaoyuan Cao; Deepa Rastogi; Mark van Zee; Ivan Pushkarsky; Hector E Munoz; Robert Damoiseaux; Dino Di Carlo; Reynold A Panettieri
Journal:  Am J Physiol Lung Cell Mol Physiol       Date:  2018-08-30       Impact factor: 5.464

  1 in total

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