Extracellular-matrix tethering regulates stem-cell fate

Trappmann, Britta; Gautrot, Julien E.; Connelly, John T.; Strange, Daniel G. T.; Li, Yuan; Oyen, Michelle L.; Cohen Stuart, Martien A.; Böhm, Heike; Li, Bojun; Vogel, Viola; Spatz, Joachim P.; Watt, Fiona M.; Huck, Wilhelm T. S.

doi:10.1038/nmat3339

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Extracellular-matrix tethering regulates stem-cell fate

MPS-Authors

/persons/resource/persons75304

Böhm, Heike
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

/persons/resource/persons76135

Spatz, Joachim P.
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

External Resource

http://www.nature.com/nmat/journal/v11/n7/pdf/nmat3339.pdf
(Any fulltext)

https://dx.doi.org/10.1038/nmat3339
(Any fulltext)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

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.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0010-4B4D-3

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.