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Mechanical regulation of cell function with geometrically modulated elastomeric substrates

An Addendum to this article was published on 28 January 2011

This article has been updated

Abstract

We report the establishment of a library of micromolded elastomeric micropost arrays to modulate substrate rigidity independently of effects on adhesive and other material surface properties. We demonstrated that micropost rigidity impacts cell morphology, focal adhesions, cytoskeletal contractility and stem cell differentiation. Furthermore, early changes in cytoskeletal contractility predicted later stem cell fate decisions in single cells.

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Figure 1: Micromolded elastomeric micropost arrays to engineer substrate rigidity.
Figure 2: Quantitative analysis of cell morphology, focal adhesions (FAs) and traction force during rigidity sensing.
Figure 3: Micropost arrays regulate and predict hMSC differentiation.

Change history

  • 28 January 2011

    In the version of this article initially published, the implication that it was the first work to decouple substrate rigidity from surface properties was incorrect, as we and others had previously reported the approach. Additional reference to previous work on micropost arrays also should have been included1. Our fabrication process, in which micropost arrays are doubly replica molded from microfabricated silicon masters, scales up production of these substrates and allows replication and distribution of disposable molds to potential users. 1. Saez, A., Buguin, A., Silberzan, P. & Ladoux, B. Biophys. J. 89, L52–L54 (2005).

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Acknowledgements

We acknowledge financial support from the US National Institutes of Health (EB00262, HL73305 and GM74048), the Army Research Office Multidisciplinary University Research Initiative, the Material Research Science and Engineering Center, the Institute for Regenerative Medicine, the Nano/Bio Interface Center, the Center for Musculoskeletal Disorders of the University of Pennsylvania and the New Jersey Center for Biomaterials. J.F. and Y.-K.W. were both partially funded by the American Heart Association postdoctoral fellowship. M.T.Y. was partially funded by the National Science Foundation Integrative Graduate Education and Research Traineeship program (DGE-0221664). We thank P. Mao and Y. Veklich for assistance with electron microscopy, D.M. Cohen for critical feedback on the manuscript and members of the Microsystems Technology Laboratories at the Massachusetts Institute of Technology for support in cleanroom fabrication.

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Contributions

J.F. and C.S.C. conceived and initiated project. J.F. and M.T.Y. designed and fabricated micropost arrays. J.F., Y.-K.W., M.T.Y., R.A.D., X.Y. and Z.L. designed and performed experiments, analyzed data and wrote the manuscript. C.S.C. supervised the project.

Corresponding author

Correspondence to Christopher S Chen.

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The authors declare no competing financial interests.

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Supplementary Figures 1–6 and Supplementary Note 1 (PDF 939 kb)

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Fu, J., Wang, YK., Yang, M. et al. Mechanical regulation of cell function with geometrically modulated elastomeric substrates. Nat Methods 7, 733–736 (2010). https://doi.org/10.1038/nmeth.1487

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