Extracellular-matrix tethering regulates stem-cell fate.
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.
Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Britta
B
Trappmann
Julien E
JE
Gautrot
John T
JT
Connelly
Daniel G T
DG
Strange
Yuan
Y
Li
Michelle L
ML
Oyen
Martien A
MA
Cohen Stuart
Heike
H
Boehm
Bojun
B
Li
Viola
V
Vogel
Joachim P
JP
Spatz
Fiona M
FM
Watt
Wilhelm T S
WT
Huck
D000180:Acrylic Resins / Q000737:chemistry / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000737:chemistry; D004129:Dimethylpolysiloxanes / Q000737:chemistry / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology; D055595:Mechanical Phenomena; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D000099166:Polyacrylamides
D000180:Acrylic Resins; D003094:Collagen; D004129:Dimethylpolysiloxanes; D000099166:Polyacrylamides; C013830:baysilon