High-Content Analysis of Cell Migration Dynamics within a Micropatterned Screening Platform.

Autor: Almeida FV; Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Gammon L; Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Laly AC; Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Pundel OJ; Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Bishop CL; Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Connelly JT; Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Jazyk: angličtina
Zdroj: Advanced biosystems [Adv Biosyst] 2019 Aug; Vol. 3 (8), pp. e1900011. Date of Electronic Publication: 2019 Jun 13.
DOI: 10.1002/adbi.201900011
Abstrakt: Cell migration is a fundamental biological process that is dynamically regulated by complex interactions between the microenvironment and intrinsic gene expression programs. Here, a high-throughput cell migration assay is developed using micropatterned and dynamically adhesive polymer brush substrates, which support highly precise and consistent control over cell-matrix interactions within a 96-well cell culture plate format. This system is combined with automated imaging and quantitation of both cell motility and organization of the F-actin cytoskeleton for high-content analysis of cell migration phenotypes. Using this platform to screen a library of 147 epigenetic inhibitors identifies a set of EZH2-specific compounds that promote cytoskeletal remodeling and accelerates keratinocyte migration through derepression of an epithelial to mesenchymal transition-like gene expression program. Together, these studies establish the high-throughput, micropatterned assay as a powerful tool for discovery of novel therapeutic targets and for dissecting complex gene-environment interactions involved in wound repair.
(© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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