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Anisotropic rigidity sensing on grating topography directs human mesenchymal stem cell elongation

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Abstract

Through mechanotransduction, cells can sense physical cues from the extracellular environment and convert them into internal signals that affect various cellular functions. For example, human mesenchymal stem cells (hMSCs) cultured on topographical gratings have been shown to elongate and differentiate to different extents depending on grating width. Using a combination of experiments and mathematical modeling, the physical parameters of substrate topography that direct cell elongation were determined. On a variety of topographical gratings with different grating widths, heights and rigidity, elongation of hMSCs was measured and a monotonic increase was observed for grating aspect ratio (crosssectional height to line-width ratio) between 0.035 and 2. The elongation was also dependent on the grating substrate rigidity over a range of 0.18–1.43 MPa. A mathematical model was developed to explain our observations by relating cell elongation to the anisotropic deformation of the gratings and how this anisotropy depends on the aspect ratio and rigidity of the gratings. Our model was in good agreement with the experimental data for the range of grating aspect ratio and substrate rigidity studied. In addition, we also showed that the percentage of aligned cells, which had a strong linear correlation with elongation for slightly elongated cells, saturated toward 100 % at higher level of cell elongation. Our results may be useful in designing gratings to elicit specific cellular responses that may depend on the extent of cell elongation.

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Acknowledgments

We thank Benjamin K.K. Teo, Seok Hong Goh, Aung Aung Kywe Moe and Soneela Ankam for their help with the experiments and engaging discussion, Benjamin K.K. Teo and Jacky W.C. Lee for the Instron tensile testing. This work was supported by the Singapore National Research Foundation under its Research Center of Excellence, Mechanobiology Institute Singapore, partially supported by the Singapore Ministry of Education Tier 1 fund (T13-0802-P04) administered through the Department of Bioengineering National University of Singapore, and A*STAR Institute of High Performance Computing. Sum Thai Wong is supported by A*STAR Scientific Staff Development Award program.

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Authors and Affiliations

  1. A*STAR Institute of High Performance Computing, 1 Fusionopolis Way #16-16, Singapore, 138632, Singapore

    Sum Thai Wong, Soo-Kng Teo & Keng-Hwee Chiam

  2. Department of Chemistry and Nano Science, Ewha Womans University, Science Building A Room #314, 11-1 Daehyun-Dong Seodaemun-Gu, Seoul, 120-750, Korea

    Sungsu Park

  3. Department of Bioengineering, National University of Singapore, 9 Engineering Drive 1 EA-03-12, Singapore, 117576, Singapore

    Sum Thai Wong & Evelyn K. F. Yim

  4. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, C/O NUHS Tower Block, Level 8, IE Kent Ridge Road, Singapore, 119228, Singapore

    Evelyn K. F. Yim

  5. Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1 #05-01, Singapore, 117411, Singapore

    Sungsu Park, Keng-Hwee Chiam & Evelyn K. F. Yim

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  1. Sum Thai Wong
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  2. Soo-Kng Teo
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Correspondence to Keng-Hwee Chiam.

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Wong, S.T., Teo, SK., Park, S. et al. Anisotropic rigidity sensing on grating topography directs human mesenchymal stem cell elongation. Biomech Model Mechanobiol 13, 27–39 (2014). https://doi.org/10.1007/s10237-013-0483-2

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