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Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue

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  • معلومة اضافية
    • بيانات النشر:
      Springer Science and Business Media LLC
    • الموضوع:
      2021
    • Collection:
      Boston University: OpenBU
    • الموضوع:
    • نبذة مختصرة :
      The structural and functional maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is essential for pharmaceutical testing, disease modeling, and ultimately therapeutic use. Multicellular 3D-tissue platforms have improved the functional maturation of hiPSC-CMs, but probing cardiac contractile properties in a 3D environment remains challenging, especially at depth and in live tissues. Using small-angle X-ray scattering (SAXS) imaging, we show that hiPSC-CMs matured and examined in a 3D environment exhibit a periodic spatial arrangement of the myofilament lattice, which has not been previously detected in hiPSC-CMs. The contractile force is found to correlate with both the scattering intensity (R 2 = 0.44) and lattice spacing (R 2 = 0.46). The scattering intensity also correlates with lattice spacing (R 2 = 0.81), suggestive of lower noise in our structural measurement than in the functional measurement. Notably, we observed decreased myofilament ordering in tissues with a myofilament mutation known to lead to hypertrophic cardiomyopathy (HCM). Our results highlight the progress of human cardiac tissue engineering and enable unprecedented study of structural maturation in hiPSC-CMs. ; 1647837 - National Science Foundation; DESC0012704 - U.S. Department of Energy ; Published version
    • File Description:
      p. 10-; Electronic-eCollection
    • ISSN:
      2096-1030
      2055-7434
    • Relation:
      Microsystems & Nanoengineering; https://www.ncbi.nlm.nih.gov/pubmed/34567727; http://dx.doi.org/10.1038/s41378-020-00234-x; J. Javor, J.K. Ewoldt, P.E. Cloonan, A. Chopra, R.J. Luu, G. Freychet, M. Zhernenkov, K. Ludwig, J.G. Seidman, C.E. Seidman, C.S. Chen, D.J. Bishop. 2021. "Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue." Microsystems & Nanoengineering, Volume 7, Issue 1, pp.10-. https://doi.org/10.1038/s41378-020-00234-x; https://hdl.handle.net/2144/48911; 0000-0002-9556-0021 (Javor, Josh); 0000-0001-8406-798X (Freychet, Guillaume); 0000-0003-3604-0672 (Zhernenkov, Mikhail); 0000-0002-7577-8701 (Ludwig, Karl); 0000-0003-2445-8449 (Chen, Christopher S); 619264
    • الرقم المعرف:
      10.1038/s41378-020-00234-x
    • Rights:
      © The Author(s) 2021. 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/. ; http://creativecommons.org/licenses/by/4.0/
    • الرقم المعرف:
      edsbas.20D45F7B