Trappmann, B and Gautrot, JE and Connelly, JT and Strange, DG and Li, Y and Oyen, ML and Cohen Stuart, MA and Boehm, H and Li, B and Vogel, V and Spatz, JP and Watt, FM and Huck, WT (2012) Extracellular-matrix tethering regulates stem-cell fate. Nat Mater, 11. pp. 642-649. ISSN 1476-1122Full text not available from this repository.
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.
|Uncontrolled Keywords:||Acrylic Resins Cell Culture Techniques Cell Differentiation Collagen Dimethylpolysiloxanes Extracellular Matrix Humans Infant, Newborn Keratinocytes Mechanical Processes Mesenchymal Stromal Cells|
|Depositing User:||Cron job|
|Date Deposited:||04 Feb 2015 22:04|
|Last Modified:||30 Mar 2015 01:25|