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Nat Mater. 2014 Oct;13(10):979-87. doi: 10.1038/nmat4051. Epub 2014 Aug 10.

Interplay of matrix stiffness and protein tethering in stem cell differentiation.

Author information

1
1] Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA [2].
2
Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA.
3
Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA.
4
1] Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA [2] Sanford Consortium for Regenerative Medicine, La Jolla, California 92037, USA.

Abstract

Stem cells regulate their fate by binding to, and contracting against, the extracellular matrix. Recently, it has been proposed that in addition to matrix stiffness and ligand type, the degree of coupling of fibrous protein to the surface of the underlying substrate, that is, tethering and matrix porosity, also regulates stem cell differentiation. By modulating substrate porosity without altering stiffness in polyacrylamide gels, we show that varying substrate porosity did not significantly change protein tethering, substrate deformations, or the osteogenic and adipogenic differentiation of human adipose-derived stromal cells and marrow-derived mesenchymal stromal cells. Varying protein-substrate linker density up to 50-fold changed tethering, but did not affect osteogenesis, adipogenesis, surface-protein unfolding or underlying substrate deformations. Differentiation was also unaffected by the absence of protein tethering. Our findings imply that the stiffness of planar matrices regulates stem cell differentiation independently of protein tethering and porosity.

PMID:
25108614
PMCID:
PMC4172528
DOI:
10.1038/nmat4051
[Indexed for MEDLINE]
Free PMC Article
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