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      Characterizing Deformability of Drug Resistant Patient-Derived Acute Lymphoblastic Leukemia (ALL) Cells Using Acoustic Tweezers

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          Abstract

          The role of cell mechanics in cancer cells is a novel research area that has resulted in the identification of new mechanisms of therapy resistance. Single beam acoustic (SBA) tweezers are a promising technology for the quantification of the mechanical phenotype of cells. Our previous study showed that SBA tweezers can be used to quantify the deformability of adherent breast cancer cell lines. The physical properties of patient-derived (primary) pre-B acute lymphoblastic leukemia (ALL) cells involved in chemotherapeutic resistance have not been widely investigated. Here, we demonstrate the feasibility of analyzing primary pre-B ALL cells from four cases using SBA tweezers. ALL cells showed increased deformability with increasing acoustic pressure of the SBA tweezers. Moreover, ALL cells that are resistant to chemotherapeutic drugs were more deformable than were untreated ALL cells. We demonstrated that SBA tweezers can quantify the deformability of nonadherent leukemia cells and discriminate this mechanical phenotype in chemotherapy-resistant leukemia cells in a contact- and label-free manner.

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          Acute Lymphoblastic Leukemia in Children.

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            Cell mechanics and the cytoskeleton.

            The ability of a eukaryotic cell to resist deformation, to transport intracellular cargo and to change shape during movement depends on the cytoskeleton, an interconnected network of filamentous polymers and regulatory proteins. Recent work has demonstrated that both internal and external physical forces can act through the cytoskeleton to affect local mechanical properties and cellular behaviour. Attention is now focused on how cytoskeletal networks generate, transmit and respond to mechanical signals over both short and long timescales. An important insight emerging from this work is that long-lived cytoskeletal structures may act as epigenetic determinants of cell shape, function and fate.
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              Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices.

              Culture of cells using various microfluidic devices is becoming more common within experimental cell biology. At the same time, a technological radiation of microfluidic cell culture device designs is currently in progress. Ultimately, the utility of microfluidic cell culture will be determined by its capacity to permit new insights into cellular function. Especially insights that would otherwise be difficult or impossible to obtain with macroscopic cell culture in traditional polystyrene dishes, flasks or well-plates. Many decades of heuristic optimization have gone into perfecting conventional cell culture devices and protocols. In comparison, even for the most commonly used microfluidic cell culture devices, such as those fabricated from polydimethylsiloxane (PDMS), collective understanding of the differences in cellular behavior between microfluidic and macroscopic culture is still developing. Moving in vitro culture from macroscopic culture to PDMS based devices can come with unforeseen challenges. Changes in device material, surface coating, cell number per unit surface area or per unit media volume may all affect the outcome of otherwise standard protocols. In this review, we outline some of the advantages and challenges that may accompany a transition from macroscopic to microfluidic cell culture. We focus on decisive factors that distinguish macroscopic from microfluidic cell culture to encourage a reconsideration of how macroscopic cell culture principles might apply to microfluidic cell culture.
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                Author and article information

                Contributors
                kkshung@usc.edu
                ymkim@chla.usc.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                24 October 2018
                24 October 2018
                2018
                : 8
                : 15708
                Affiliations
                [1 ]ISNI 0000 0001 2156 6853, GRID grid.42505.36, Department of Biomedical Engineering and NIH Ultrasonic Transducer Resource Center, , University of Southern California, ; 1042 Downey Way, Los Angeles, CA 90089 USA
                [2 ]ISNI 0000 0001 2156 6853, GRID grid.42505.36, Department of Pediatrics, Division of Hematology, Oncology, Blood and Marrow Transplantation, Children’s Hospital Los Angeles, , University of Southern California, ; 4650 Sunset Blvd, Los Angeles, CA 90027 USA
                [3 ]ISNI 0000 0001 0742 4007, GRID grid.49100.3c, Department of Creative IT Engineering and Future IT Innovation Laboratory, , Pohang University of Science and Technology, ; 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673 Republic of Korea
                Author information
                http://orcid.org/0000-0002-5410-8821
                http://orcid.org/0000-0002-4182-7130
                http://orcid.org/0000-0002-5338-359X
                Article
                34024
                10.1038/s41598-018-34024-3
                6200731
                30356155
                89ba0b50-7233-40c5-bfa2-19b1ff131550
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 January 2018
                : 5 October 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000054, U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI);
                Award ID: CA172896
                Award Recipient :
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