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Quantifying 3D cell-matrix interactions during mitosis and the effect of anticancer drugs on the interactions

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Abstract

The mechanical force between cells and the extracellular microenvironment is crucial to many physiological processes such as cancer metastasis and stem cell differentiation. Mitosis plays an essential role in all these processes and thus an in-depth understanding of forces during mitosis gains insight into disease diagnosis and disease treatment. Here, we develop a traction force microscope method based on monolayer fluorescent beads for measuring the weak traction force (tens of Pa) of mitotic cells in three dimensions. We quantify traction forces of human ovarian granulosa (KGN) cells exerted on the extracellular matrix throughout the entire cell cycle in three dimensions. Our measurements reveal how forces vary during the cell cycle, especially during cell division. Furthermore, we study the effect of paclitaxel (PTX) and nocodazole (NDZ) on mitotic KGN cells through the measurement of traction forces. Our results show that mitotic cells with high concentrations of PTX exert a larger force than those with high concentrations of NDZ, which proved to be caused by changes in the structure and number of microtubules. These findings reveal the key functions of microtubule in generating traction forces during cell mitosis and explain how dividing cells regulate themselves in response to anti-mitosis drugs. This work provides a powerful tool for investigating cell-matrix interactions during mitosis and may offer a potential way to new therapies for cancer.

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Acknowledgements

The authors gratefully acknowledge financial support from the National Natural Science Foundation of China (Nos. 11872355, 11627803, 12072339, and 11872354) and the Strategic Priority Research Program of the Chinese Academy of Science (No. XDB22040502).

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Author notes

  1. Yongman Liu and Jianye Wang contributed equally to this work.

Authors and Affiliations

  1. CAS Key Laboratory of Mechanical Behavior and Design of Material, Department of Modern Mechanics, CAS Center for Excellence in Complex System Mechanics, University of Science and Technology of China, Hefei, 230027, China

    Yongman Liu, Yong Su, Xiaohai Xu, Kainan Mei, Shihai Lan, Shubo Zhang, Xiaoping Wu, Qingchuan Zhang & Shangquan Wu

  2. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China

    Jianye Wang & Yunxia Cao

  3. Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei, 230022, China

    Jianye Wang & Yunxia Cao

  4. Department of Chemical Physics, University of Science and Technology of China, Hefei, 230026, China

    Hong Liu

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  1. Yongman Liu
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  2. Jianye Wang
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  3. Yong Su
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  5. Hong Liu
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  9. Xiaoping Wu
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  10. Yunxia Cao
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  11. Qingchuan Zhang
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Correspondence to Yunxia Cao, Qingchuan Zhang or Shangquan Wu.

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Liu, Y., Wang, J., Su, Y. et al. Quantifying 3D cell-matrix interactions during mitosis and the effect of anticancer drugs on the interactions. Nano Res. 14, 4163–4172 (2021). https://doi.org/10.1007/s12274-021-3357-4

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  • DOI: https://doi.org/10.1007/s12274-021-3357-4

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