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Soft substrate and decreased cytoskeleton contractility promote coupling and morphology maintenance of pluripotent stem cells

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Abstract

The mechanical microenvironment affects the morphology and mechanical properties of cells, and it also plays an important role in cell functions. Pluripotent stem cells (PSCs) grow as multicellular colonies, and the coupling effects of cell–cell and cell-extracellular matrix interactions are complex but necessary for the formations and functions of tissues. This paper uses the finite element method to establish a three-dimensional calculation model of a pair of deformed PSCs in contact with each other and considers the growth and depolymerization of actin filaments. Then the effects of substrate stiffness on the morphology of cells and nuclei and the rearrangement of cytoskeleton are demonstrated. As the substrate becomes softer, the nuclei become loose and round, and the actin filaments will be assembled at a lower level, which could promote the formation of compacted cell colony while having a positive effect on maintaining pluripotency and inducing reprogramming efficiency. In addition, stronger activation of cytoskeleton contractility will compress the cytoplasm and nuclei. The cell mechanics model proposed in this paper provides a strategy for studying the cell morphology and cytoskeleton response of the two-cell system under different biophysical stimuli, and also lays the foundation for the further research on more mechanical factors of cell pluripotency.

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Acknowledgements

We thank Y.P.Cao (Tsinghua University) and Z.H.Zhao (Tsinghua University) for discussions during the preparation of this paper.This work was supported by the National Key R&D Program of China (2017YFA0506500, 2016YFC1102203, and 2016YFC1101100), the National Natural Science Foundation of China (31370018, 11972206, 11902114, 11421202, 11827803, and 11902020), Fundamental Research Funds for the Central Universities (ZG140S1971), and Young Elite Scientist Sponsorship Program by CAST (YESS 2015QNRC001).

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    Authors and Affiliations

    1. Key Laboratory for Biomechanics and Mechanobiology of the Ministry of Education, Institute of Nanotechnology for Single Cell Analysis, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China

      Meihong Lu, Jialing Cao, Yuanyuan Zhai, Peng Zhao, Jie Yao, Jing Du & Yubo Fan

    2. Institute of Biomechanics and Medical Engineering, Department of Mechanical Engineering, School of Aerospace, Tsinghua University, Beijing, 100084, China

      Meihong Lu

    3. Sino-French Engineer School, Beihang University, Beijing, 100083, China

      Jialing Cao

    4. School of Material Science & Engineering, Beijing Institute of Fashion Technology, Beijing, 100029, China

      Yuanyuan Zhai & Yan Gong

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    1. Meihong Lu
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    Contributions

    M.H.Lu, J.L.Cao, J.Du and Y.B.Fan designed the study and prepared the paper. M.H.Lu, J.L.Cao and J.Yao did mechanical analysis. Y.P.Cao and P.Zhao performed experiments. J.Du, and Y.B.Fan conceived and supervised this project.

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    Correspondence to Jing Du or Yubo Fan.

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    Executive Editor: Hongyuan Jiang.

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    Meihong Lu and Jialing Cao contributed equally.

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    Lu, M., Cao, J., Zhai, Y. et al. Soft substrate and decreased cytoskeleton contractility promote coupling and morphology maintenance of pluripotent stem cells. Acta Mech. Sin. 37, 1520–1529 (2021). https://doi.org/10.1007/s10409-021-01118-7

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    • DOI: https://doi.org/10.1007/s10409-021-01118-7

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