Simulated microgravity attenuates myogenesis and contractile function of 3D engineered skeletal muscle tissues

Zhanping Ren; Eun Hyun Ahn; Minjae Do; Devin B Mair; Amir Monemianesfahani; Peter H U Lee; Deok-Ho Kim

doi:10.1038/s41526-024-00353-z

Simulated microgravity attenuates myogenesis and contractile function of 3D engineered skeletal muscle tissues

NPJ Microgravity. 2024 Feb 16;10(1):18. doi: 10.1038/s41526-024-00353-z.

Authors

Zhanping Ren¹, Eun Hyun Ahn², Minjae Do², Devin B Mair², Amir Monemianesfahani², Peter H U Lee^{3

4}, Deok-Ho Kim^{5

6

7

8}

Affiliations

¹ Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21205, USA.
² Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21205, USA.
³ Department of Cardiothoracic Surgery, Southcoast Health, Fall River, MA, 02720, USA. Peter_Lee@brown.edu.
⁴ Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, 02912, USA. Peter_Lee@brown.edu.
⁵ Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21205, USA. dhkim@jhu.edu.
⁶ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21205, USA. dhkim@jhu.edu.
⁷ Department of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA. dhkim@jhu.edu.
⁸ Center for Microphysiological Systems, Johns Hopkins University, Baltimore, MD, 21205, USA. dhkim@jhu.edu.

Abstract

While the effects of microgravity on inducing skeletal muscle atrophy have been extensively studied, the impacts of microgravity on myogenesis and its mechanisms remain unclear. In this study, we developed a microphysiological system of engineered muscle tissue (EMT) fabricated using a collagen / Matrigel composite hydrogel and murine skeletal myoblasts. This 3D EMT model allows non-invasive quantitative assessment of contractile function. After applying a 7-day differentiation protocol to induce myotube formation, the EMTs clearly exhibited sarcomerogenesis, myofilament formation, and synchronous twitch and tetanic contractions with electrical stimuli. Using this 3D EMT system, we investigated the effects of simulated microgravity at 10^-3G on myogenesis and contractile function utilizing a random positioning machine. EMTs cultured for 5 days in simulated microgravity exhibited significantly reduced contractile forces, myofiber size, and differential expression of muscle contractile, myogenesis regulatory, and mitochondrial biogenesis-related proteins. These results indicate simulated microgravity attenuates myogenesis, resulting in impaired muscle function.

Abstract

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