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Extracellular-matrix tethering regulates stem-cell fate

2012; Nature Portfolio; Volume: 11; Issue: 7 Linguagem: Inglês

10.1038/nmat3339

1476-4660

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,

Bone Tissue Engineering Materials

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. The spreading and differentiation of stem cells is influenced by the mechanical properties—in particular by the stiffness—of the extracellular matrix. Now, experiments on epidermal stem cells cultured on substrates with a covalently attached collagen coating show that stem cells sense the stiffness of the substrate through the anchoring density of collagen fibres.