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Multi-well plate cell contraction assay detects negatively correlated cellular responses to pharmacological inhibitors in contractility and migration
Institution:1. Department of Biomolecular Sciences, Tohoku University, Japan;2. Department of Biomedical Engineering, Tohoku University, Japan;3. Department of Bioengineering and Robotics, Tohoku University, Japan;1. Flaum Eye Institute, USA;2. Department of Medicine, University of Rochester, Rochester, NY, USA;1. Department of Microbiology, Inha University School of Medicine, Incheon, 22212, South Korea;2. Division of Tumor Immunology, National Cancer Center, Goyang, 10408, South Korea;3. Department of Otorhinolaryngology-Head and Neck Surgery, Inha University School of Medicine, Incheon, 22212, South Korea;1. Department of Pharmacology, Peripheral Neuropathy Research Center (PNRC), Dong-A University College of Medicine, Busan, 49201, South Korea;2. Department of Biochemistry, Peripheral Neuropathy Research Center (PNRC), Dong-A University College of Medicine, Busan, 49201, South Korea;3. Department of Neurology, SAIHST, Sungkyunkwan University School of Medicine, Seoul, 06351, South Korea;1. Cheeloo College of Medicine, Shandong University, Jinan, 250100, PR China;2. School of Basic Medical Sciences, Shandong University, Jinan, 250100, PR China
Abstract:To enable large-scale screening of signaling molecules and drugs that regulate cellular contractility-associated mechanotransduction, we previously modified, particularly in terms of the capability of efficiently collecting big data, conventional methodologies using wrinkled substrates to determine the cellular contractility. Here, we present a new system to perform the wrinkle-based cell force assay in a multi-well plate format conformed to standardized geometric configurations and compatible with available technologies such as automated plate readers. With this highly improved throughput in terms of hardware as well as software using a deep learning-based technology, we evaluated the effect of treating cells with various types of pharmacological inhibitors on the cellular contractility. We found opposite responses of cells to the inhibitors between the contractility and collective migration activities. While similar inverse relationships between the contractility and migration have been reported in separate studies, our results here with the high-throughput screening system more broadly generalized these observations.
Keywords:Cell assay  Cell contractility  Deep learning  High-throughput screening  Mechanobiology
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