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Single Cell Hydrodynamic Stretching and Microsieve Filtration Reveal Genetic, Phenotypic and Treatment-Related Links to Cellular Deformability

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Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, Singapore
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Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University Singapore, 21 Nanyang Link, Singapore 637371, Singapore
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Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore 138669, Singapore
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DKFZ-Division Translational Neurooncology at the WTZ, DKTK partner site, University Hospital Essen, 45147 Essen, Germany
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Lucence Diagnostics Pte Ltd., 211 Henderson Road, Henderson Industrial Park, Singapore 159552, Singapore
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Institute for Physics, Faculty of Natural Sciences, Otto-von-Guericke University of Magdeburg, 39106 Magdeburg, Germany
*
Authors to whom correspondence should be addressed.
Micromachines 2020, 11(5), 486; https://doi.org/10.3390/mi11050486
Received: 30 March 2020 / Revised: 6 May 2020 / Accepted: 8 May 2020 / Published: 9 May 2020
(This article belongs to the Special Issue Micro/Nanofluidic Devices for Single Cell Analysis, Volume II)
Deformability is shown to correlate with the invasiveness and metastasis of cancer cells. Recent studies suggest epithelial-to-mesenchymal transition (EMT) might enable cancer metastasis. However, the correlation of EMT with cancer cell deformability has not been well elucidated. Cellular deformability could also help evaluate the drug response of cancer cells. Here, we combine hydrodynamic stretching and microsieve filtration to study cellular deformability in several cellular models. Hydrodynamic stretching uses extensional flow to rapidly quantify cellular deformability and size with high throughput at the single cell level. Microsieve filtration can rapidly estimate relative deformability in cellular populations. We show that colorectal cancer cell line RKO with the mesenchymal-like feature is more flexible than the epithelial-like HCT116. In another model, the breast epithelial cells MCF10A with deletion of the TP53 gene are also significantly more deformable compared to their isogenic wildtype counterpart, indicating a potential genetic link to cellular deformability. We also find that the drug docetaxel leads to an increase in the size of A549 lung cancer cells. The ability to associate mechanical properties of cancer cells with their phenotypes and genetics using single cell hydrodynamic stretching or the microsieve may help to deepen our understanding of the basic properties of cancer progression. View Full-Text
Keywords: cancer metastasis; deformability; epithelial to mesenchymal transition; TP53 genes; chemotherapy drug; microfluidic hydrodynamic stretching; microsieve cancer metastasis; deformability; epithelial to mesenchymal transition; TP53 genes; chemotherapy drug; microfluidic hydrodynamic stretching; microsieve
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Li, F.; Cima, I.; Vo, J.H.; Tan, M.-H.; Ohl, C.D. Single Cell Hydrodynamic Stretching and Microsieve Filtration Reveal Genetic, Phenotypic and Treatment-Related Links to Cellular Deformability. Micromachines 2020, 11, 486.

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