Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels
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Open Access
- 24 March 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Materials
- Vol. 12 (5), 458-465
- https://doi.org/10.1038/nmat3586
Abstract
Although cell–matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular traction, independently of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). Moreover, switching the permissive hydrogel to a restrictive state through delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Furthermore, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment.Keywords
This publication has 40 references indexed in Scilit:
- Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanicsNature Communications, 2012
- Mechanical regulation of cell function with geometrically modulated elastomeric substratesNature Methods, 2010
- Intrinsic extracellular matrix properties regulate stem cell differentiationJournal of Biomechanics, 2010
- Control of Stem Cell Fate by Physical Interactions with the Extracellular MatrixCell Stem Cell, 2009
- Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin systemJournal of Cellular and Molecular Medicine, 2007
- Matrix Elasticity Directs Stem Cell Lineage SpecificationCell, 2006
- Synthetic hydrogel niches that promote hMSC viabilityMatrix Biology, 2005
- RGD‐grafted poly‐l‐lysine‐graft‐(polyethylene glycol) copolymers block non‐specific protein adsorption while promoting cell adhesionBiotechnology & Bioengineering, 2003
- Anchorage dependence, integrins, and apoptosisCell, 1994
- The extracellular matrix as a cell survival factor.Molecular Biology of the Cell, 1993