Extracellular-matrix Tethering Regulates Stem-cell Fate

Overview

Journal Nat Mater

Date 2012 May 29

PMID 22635042

Citations 559

Authors

Britta Trappmann

Julien E Gautrot

John T Connelly

Daniel G T Strange

Yuan Li

Michelle L Oyen

Martien A Cohen Stuart

Heike Boehm

Bojun Li

Viola Vogel

Joachim P Spatz

Fiona M Watt

Wilhelm T S Huck

Affiliations

Soon will be listed here.

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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