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Understanding Nanotopography Induced Stem Cell Differentiation: A Focus on Focal Adhesion Kinase

  • Benjamin Kim Kiat Teo
  • Sum Thai Wong
  • Choon Kiat Lim
  • Terrence Y. S. Kung
  • Chong Hao Yap
  • Yamini Ramgopal
  • Lewis H. Romer
  • Evelyn K. F. Yim
Part of the IFMBE Proceedings book series (IFMBE, volume 43)

Abstract

Biophysical cues, such as nanotopography, have been shown to be integral for tissue regeneration and embryogenesis in the stem cell niche. 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 250 nm nanogratings on polydimethylsiloxane, hMSCs developed aligned stress fibers and showed an upregulation of neurogenic differentiation markers. In addition, our mechanistic study confirmed that this regulation was dependent upon actomyosin contractility, suggesting a direct force-dependent mechanism. 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. These findings suggest that hMSC sense and transduce nanotopo-graphical signals through focal adhesions and actomyosin cytoskeleton contractility to induce differential gene expression.

Keywords

Mesenchymal stem cell cell signaling FAK differentiation focal adhesions physical cues 

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Benjamin Kim Kiat Teo
    • 1
    • 2
  • Sum Thai Wong
    • 1
    • 3
  • Choon Kiat Lim
    • 2
  • Terrence Y. S. Kung
    • 2
  • Chong Hao Yap
    • 2
  • Yamini Ramgopal
    • 2
  • Lewis H. Romer
    • 4
  • Evelyn K. F. Yim
    • 1
    • 2
    • 5
  1. 1.Department of BioengineeringNational University of SingaporeSingaporeSingapore
  2. 2.Mechanobiology Institute SingaporeNational University of SingaporeSingaporeSingapore
  3. 3.Institute of High Performance ComputingA*STARSingaporeSingapore
  4. 4.Department of Anesthesiology and Critical Care Medicine, Cell Biology, Biomedical Engineering, Pediatrics and Center for Cell DynamicsJohns Hopkins University School of MedicineBaltimoreUSA
  5. 5.Department of SurgeryNational University of SingaporeSingaporeSingapore

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