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  Extracellular-matrix tethering regulates stem-cell fate

Trappmann, B., Gautrot, J. E., Connelly, J. T., Strange, D. G. T., Li, Y., Oyen, M. L., et al. (2012). Extracellular-matrix tethering regulates stem-cell fate. Nature Materials, 11(7), 642-649. doi:10.1038/nmat3339.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-4B4D-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-5E84-E
Genre: Journal Article

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Trappmann, Britta, Author
Gautrot, Julien E., Author
Connelly, John T., Author
Strange, Daniel G. T., Author
Li, Yuan, Author
Oyen, Michelle L., Author
Cohen Stuart, Martien A., Author
Böhm, Heike1, 2, Author              
Li, Bojun, Author
Vogel, Viola, Author
Spatz, Joachim P.1, 2, Author              
Watt, Fiona M., Author
Huck, Wilhelm T. S., Author
Affiliations:
1Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_2364731              
2Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany, ou_persistent22              

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 Abstract: To investigate how substrate properties influence stem-cell fate, we cultured single human epidermal stem cells on polydimethylsiloxane (PDMS) and polyacrylamide (PAAm) hydrogel surfaces, 0.1 kPa-2.3 MPa in stiffness, with a covalently attached collagen coating. Cell spreading and differentiation were unaffected by polydimethylsiloxane stiffness. However, cells on polyacrylamide of low elastic modulus (0.5 kPa) could not form stable focal adhesions and differentiated as a result of decreased activation of the extracellular-signal-related kinase (ERK)/mitogen-activated protein kinase (MAPK) signalling pathway. The differentiation of human mesenchymal stem cells was also unaffected by PDMS stiffness but regulated by the elastic modulus of PAAm. Dextran penetration measurements indicated that polyacrylamide substrates of low elastic modulus were more porous than stiff substrates, suggesting that the collagen anchoring points would be further apart. We then changed collagen crosslink concentration and used hydrogel-nanoparticle substrates to vary anchoring distance at constant substrate stiffness. Lower collagen anchoring density resulted in increased differentiation. We conclude that stem cells exert a mechanical force on collagen fibres and gauge the feedback to make cell-fate decisions.

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Language(s): eng - English
 Dates: 2012-05-272012-07-01
 Publication Status: Published in print
 Pages: 9
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 Rev. Type: Peer
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Title: Nature Materials
  Abbreviation : Nat. Mater.
Source Genre: Journal
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Publ. Info: London, UK : Nature Pub. Group
Pages: - Volume / Issue: 11 (7) Sequence Number: - Start / End Page: 642 - 649 Identifier: ISSN: 1476-1122
CoNE: https://pure.mpg.de/cone/journals/resource/111054835734000