Skip to main content
SpringerLink
Log in

Designing Elastic Modulus of Cell Culture Substrate to Regulate YAP and RUNX2 Localization for Controlling Differentiation of Human Mesenchymal Stem Cells

  • Original Papers
  • Published:
Analytical Sciences Aims and scope Submit manuscript

Abstract

To establish a guideline for the design of cell culture substrates to control human mesenchymal stem cell (MSC) differentiation, we quantitatively characterized the heterogeneity in the responsiveness of MSCs to the elastic modulus of culture substrates. We analyzed the elastic modulus-dependent dynamics of a mechanotransducer, YAP, and an osteogenic differentiation factor, RUNX2, in three different MSC lots using a styrenated gelatin gel with controllable elastic modulus. The percentage of cells with YAP in the nucleus increased linearly with increases in the elastic modulus, reaching a plateau at 10 kPa for all the lots analyzed. The increase in the percentage with the substrate elastic modulus was described by the same linear function. The percentage of cells with RUNX2 nuclear localization also increased linearly with increases in the substrate elastic modulus, plateauing at 5 kPa, although the regression lines to the linearly increasing regions varied between lots. These similarities and differences in YAP and RUNX2 dynamics among cell populations are basis to design the substrate elastic modulus to manipulate YAP and RUNX2 localizations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. L. Li, J. Eyckmans, and C. S. Chen, Nat. Mater., 2017, 16, 1164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. H. Miyoshi, K. Suzuki, J. Ju, J. S. Ko, T. Adachi, and Y. Yamagata, Anal. Sci., 2016, 32, 1207.

    Article  CAS  PubMed  Google Scholar 

  3. T. Yamashita, T. Nishina, I. Matsushita, and R. Sudo, Anal. Sci., 2020, 36, 1015.

    Article  CAS  PubMed  Google Scholar 

  4. J. Lee, A. A. Abdeen, T. H. Huang, and K. A. Kilian, J. Mech. Behav. Biomed. Mater., 2014, 38, 209.

    Article  CAS  PubMed  Google Scholar 

  5. A. J. Engler, S. Sen, H. L. Sweeney, and D. E. Discher, Cell, 2006, 126, 677.

    Article  CAS  PubMed  Google Scholar 

  6. C. Yang, M. W. Tibbitt, L. Basta, and K. S. Anseth, Nat. Mater., 2014, 13, 645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. J. Lee, A. A. Abdeen, and K. A. Kilian, Sci. Rep., 2014, 4, 5188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. M. F. Pittenger, D. E. Discher, B. M. Péault, D. G. Phinney, J. M. Hare, and A. I. Caplan, npj Regener. Med., 2019, 4, 22.

    Article  Google Scholar 

  9. D. Sipp, G. P. Robey, and L. Turner, Nature, 2018, 561, 455.

    Article  CAS  PubMed  Google Scholar 

  10. S. Dupont, L. Morsut, M. Aragona, E. Enzo, S. Giulitti, M. Cordenonsi, F. Zanconato, J. Le Digabel, M. Forcato, S. Bicciato, N. Elvassore, and S. Piccolo, Nature, 2011, 474, 179.

    Article  CAS  PubMed  Google Scholar 

  11. K. Wada, K. Itoga, T. Okano, S. Yonemura, and H. Sasaki, Development, 2011, 138, 3907.

    Article  CAS  PubMed  Google Scholar 

  12. S. Piccolo, S. Dupont, and M. Cordenonsi, Physiol. Rev., 2014, 94, 1287.

    Article  CAS  PubMed  Google Scholar 

  13. M. K. Kim, J. W. Jang, and S. C. Bae, BMB Rep., 2018, 51, 126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. S. K. Zaidi, A. Javed, J. Y. Choi, A. J.. van Wijnen, J. L. Stein, J. B. Lian, and G. S. Stein, J. Cell Sci., 2001, 114, 3093.

    Article  CAS  PubMed  Google Scholar 

  15. I. Han, B.-S. Kwon, H.-K. Park, and K. S. Kim, Int. Neurourol. J., 2017, 21, S24.

    Article  PubMed  PubMed Central  Google Scholar 

  16. M. Kawagishi-Hotta, S. Hasegawa, T. Igarashi, T. Yamada, M. Takahashi, S. Numata, T. Kobayashi, Y. Iwata, M. Arima, N. Yamamoto, A. Yagami, S. Nakata, T. Uzawa, K. Matsunaga, K. Sugiura, and H. Akamatsu, Regener. Ther., 2017, 6, 29.

    Article  Google Scholar 

  17. Y. Sakaguchi, I. Sekiya, K. Yagishita, and T. Muneta, Arthritis Rheum., 2005, 52, 2521.

    Article  PubMed  Google Scholar 

  18. Y.-H. K. Yang, C. R. Ogando, C. Wang See, T.-Y. Chang, and G. A. Barabino, Stem Cell Res. Ther., 2018, 9, 131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. T. Kuboki and S. Kidoaki, Methods Mol. Biol., 2016, 1416, 425.

    Article  CAS  PubMed  Google Scholar 

  20. A. R. Killaars, J. C. Grim, C. J. Walker, E. A. Hushka, T. E. Brown, and K. S. Anseth, Adv. Sci. (Weinh), 2019, 6, 1801483.

    Article  PubMed  Google Scholar 

  21. B. D. Cosgrove, K. L. Mui, T. P. Driscoll, S. R. Caliari, K. D. Mehta, R. K. Assoian, J. A. Burdick, and R. L. Mauck, Nat. Mater., 2016, 15, 1297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Q. Chen, P. Shou, C. Zheng, M. Jiang, G. Cao, Q. Yang, J. Cao, N. Xie, T. Velletri, X. Zhang, C. Xu, L. Zhang, H. Yang, J. Hou, Y. Wang, and Y. Shi, Cell Death Differ., 2016, 23, 1128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. M. Yamazaki, H. Fujie, and H. Miyoshi, J. Biomech. Sci. Eng., 2020, 15, 2.

    Article  Google Scholar 

  24. G. Nardone, J. Oliver-De La Cruz, J. Vrbsky, C. Martini, J. Pribyl, P. Skládal, M. Pešl, G. Caluori, S. Pagliari, F. Martino, Z. Maceckova, M. Hajduch, A. Sanz-Garcia, N. M. Pugno, G. B. Stokin, and G. Forte, Nat. Commun., 2017, 8, 15321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. S. Walcott and S. X. Sun, Proc. Natl. Acad. Sci. U. S. A., 2010, 107, 7757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. H. Gerardo, A. Lima, J. Carvalho, J. R. D. Ramos, S. Couceiro, R. D. M. Travasso, R. Pires das Neves, and M. Grãos, Sci. Rep., 2019, 9, 9086.

    Article  PubMed  PubMed Central  Google Scholar 

  27. M. Bruderer, R. G. Richards, M. Alini, and M. J. Stoddart, Eur. Cells Mater., 2014, 28, 269.

    Article  CAS  Google Scholar 

  28. M. M. Musri, R. Gomis, and M. Párrizas, Organogenesis, 2010, 6, 15.

    Article  PubMed  PubMed Central  Google Scholar 

  29. C. Ge, W. P. Cawthorn, Y. Li, G. Zhao, O. A. MacDougald, and R. T. Franceschi, J. Cell. Physiol., 2016, 231, 587.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. M. P. Lutolf and J. A. Hubbell, Nat. Biotechnol., 2005, 23, 47.

    Article  CAS  PubMed  Google Scholar 

  31. S. Lee, A. E. Stanton, X. Tong, and F. Yang, Biomaterials, 2019, 202, 26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. B. Trappmann, J. E. Gautrot, J. T. Connelly, D. G. Strange, Y. Li, M. L. Oyen, M. A. Cohen Stuart, H. Boehm, B. Li, V. Vogel, J. P. Spatz, F. M. Watt, and W. T. Huck, Nat. Mater., 2012, 11, 642.

    Article  CAS  PubMed  Google Scholar 

  33. C. D. Reyes and A. J. García, J. Biomed. Mater. Res., Part A, 2003, 65, 511.

    Article  Google Scholar 

  34. J. Z. Kechagia, J. Ivaska, and P. Roca-Cusachs, Nat. Rev. Mol. Cell Biol., 2019, 20, 457.

    Article  CAS  PubMed  Google Scholar 

  35. H. Yukawa and Y. Baba, Anal. Sci., 2018, 34, 525.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Mechanical Systems and Engineering Graduate School Systems Design, Tokyo Metropolitan University, 1-1 Minamiosawa, Hachioji, Tokyo, 192-0397, Japan

    Masashi Yamazaki, Hiromichi Fujie & Hiromi Miyoshi

  2. Laboratory of Biomedical and Biophysical Chemistry, Institute for Materials Chemistry and Engineering, Kyushu University, 744 Motooka, Nishi, Fukuoka, 819-0395, Japan

    Satoru Kidoaki

Authors
  1. Masashi Yamazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Satoru Kidoaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiromichi Fujie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiromi Miyoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiromi Miyoshi.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamazaki, M., Kidoaki, S., Fujie, H. et al. Designing Elastic Modulus of Cell Culture Substrate to Regulate YAP and RUNX2 Localization for Controlling Differentiation of Human Mesenchymal Stem Cells. ANAL. SCI. 37, 447–451 (2021). https://doi.org/10.2116/analsci.20SCP02

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2116/analsci.20SCP02

Keywords

Search

Navigation