Extracellular-matrix tethering regulates stem-cell fate

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

doi:10.1038/nmat3339

Extracellular-matrix tethering regulates stem-cell fate

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

Centre for Stem Cells & Regenerative Medicine

Research output: Contribution to journal › Article › peer-review

1306 Citations (Scopus)

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.

Original language	English
Pages (from-to)	642-9
Number of pages	8
Journal	NATURE MATERIALS
Volume	11
Issue number	7
DOIs	https://doi.org/10.1038/nmat3339
Publication status	Published - Jul 2012

Keywords

Dimethylpolysiloxanes
Mesenchymal Stromal Cells
Acrylic Resins
Humans
Extracellular Matrix
Mechanical Processes
Infant, Newborn
Cell Culture Techniques
Cell Differentiation
Keratinocytes
Collagen

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title = "Extracellular-matrix tethering regulates stem-cell fate",

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.",

keywords = "Dimethylpolysiloxanes, Mesenchymal Stromal Cells, Acrylic Resins, Humans, Extracellular Matrix, Mechanical Processes, Infant, Newborn, Cell Culture Techniques, Cell Differentiation, Keratinocytes, Collagen",

author = "Britta Trappmann and Gautrot, {Julien E} and Connelly, {John T} and Strange, {Daniel G T} and Yuan Li and Oyen, {Michelle L} and {Cohen Stuart}, {Martien A} and Heike Boehm and Bojun Li and Viola Vogel and Spatz, {Joachim P} and Watt, {Fiona M} and Huck, {Wilhelm T S}",

year = "2012",

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doi = "10.1038/nmat3339",

language = "English",

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T1 - Extracellular-matrix tethering regulates stem-cell fate

AU - Trappmann, Britta

AU - Gautrot, Julien E

AU - Connelly, John T

AU - Strange, Daniel G T

AU - Li, Yuan

AU - Oyen, Michelle L

AU - Cohen Stuart, Martien A

AU - Boehm, Heike

AU - Li, Bojun

AU - Vogel, Viola

AU - Spatz, Joachim P

AU - Watt, Fiona M

AU - Huck, Wilhelm T S

PY - 2012/7

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N2 - 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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KW - Mesenchymal Stromal Cells

KW - Acrylic Resins

KW - Humans

KW - Extracellular Matrix

KW - Mechanical Processes

KW - Infant, Newborn

KW - Cell Culture Techniques

KW - Cell Differentiation

KW - Keratinocytes

KW - Collagen

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DO - 10.1038/nmat3339

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JO - NATURE MATERIALS

JF - NATURE MATERIALS

IS - 7

ER -

Extracellular-matrix tethering regulates stem-cell fate

Abstract

Keywords

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