Nanotopography modulates mechanotransduction of stem cells and induces differentiation through focal adhesion kinase

Benjamin Kim Kiat Teo, Sum Thai Wong, Choon Kiat Lim, Terrence Y.S. Kung, Chong Hao Yap, Yamini Ramagopal, Lewis H. Romer, Evelyn K.F. Yim

Research output: Contribution to journalArticle

Abstract

Regulated biophysical cues, such as nanotopography, have been shown to be integral for tissue regeneration and embryogenesis in the stem cell niche. Tissue homeostasis involves the interaction of multipotent cells with nanoscaled topographical features in their ECM to regulate aspects of cell behavior. Synthetic nanostructures can drive specific cell differentiation, but the sensing mechanisms for nanocues remain poorly understood. Here, we report that nanotopography-induced human mesenchymal stem cell (hMSC) differentiation through cell mechanotransduction is modulated by the integrin-activated focal adhesion kinase (FAK). On nanogratings with 250 nm line width on polydimethylsiloxane, hMSCs developed aligned stress fibers and showed an upregulation of neurogenic and myogenic differentiation markers. The observed cellular focal adhesions within these cells were also significantly smaller and more elongated on the nanogratings compared to microgratings or unpatterned control. In addition, our mechanistic study confirmed that this regulation was dependent upon actomyosin contractility, suggesting a direct force-dependent mechanism. The topography-induced differentiation was observed on different ECM compositions but the response was not indicative of a direct ECM-induced hMSC differentiation pathway. FAK phosphorylation was required for topography-induced hMSC differentiation while FAK overexpression overruled the topographical cues in determining cell lineage bias. The results indicated that FAK activity had a direct impact on topography-induced gene expression, and that this effect of FAK was independent of cell shape. These findings suggest that hMSC sense and transduce nanotopographical signals through focal adhesions and actomyosin cytoskeleton contractility to induce differential gene expression.

Original languageEnglish (US)
Pages (from-to)4785-4798
Number of pages14
JournalACS Nano
Volume7
Issue number6
DOIs
StatePublished - Jun 25 2013

Keywords

  • FAK
  • cell signaling
  • differentiation
  • focal adhesions
  • mesenchymal stem cell
  • nanotopography
  • physical cues

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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  • Cite this

    Teo, B. K. K., Wong, S. T., Lim, C. K., Kung, T. Y. S., Yap, C. H., Ramagopal, Y., Romer, L. H., & Yim, E. K. F. (2013). Nanotopography modulates mechanotransduction of stem cells and induces differentiation through focal adhesion kinase. ACS Nano, 7(6), 4785-4798. https://doi.org/10.1021/nn304966z