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2009   Volume No 18 – pages 1-14

Title: Substrate stiffness affects early differentiation events in embryonic stem cells

Author: ND Evans, C Minelli, E Gentleman, V LaPointe, SN Patankar, M Kallivretaki, X Chen, CJ Roberts, MM Stevens

Address: Dept Materials, Royal School of Mines, Imperial College, Prince Consort Road, London SW7 2BP, U.K.

E-mail: m.stevens at imperial.ac.uk

Key Words: Embryonic stem cells; cellular mechanotransduction; gastrulation; extracellular matrix; differentiation; mammalian development.

Publication date: September 21st 2009

Abstract: Embryonic stem cells (ESC) are both a potential source of cells for tissue replacement therapies and an accessible tool to model early embryonic development. Chemical factors such as soluble growth factors and insoluble components of the extracellular matrix are known to affect the differentiation of murine ESCs. However, there is also evidence to suggest that undifferentiated cells can both sense the mechanical properties of their environment and differentiate accordingly. By growing ESCs on flexible polydimethylsiloxane substrates with varying stiffness, we tested the hypothesis that substrate stiffness can influence ESC differentiation. While cell attachment was unaffected by the stiffness of the growth substrate, cell spreading and cell growth were all increased as a function of substrate stiffness. Similarly, several genes expressed in the primitive streak during gastrulation and implicated in early mesendoderm differentiation, such as Brachyury, Mixl1 and Eomes, were upregulated in cell cultures on stiffer compared to softer substrates. Finally, we demonstrated that osteogenic differentiation of ESCs was enhanced on stiff substrates compared to soft substrates, illustrating that the mechanical environment can play a role in both early and terminal ESC differentiation. Our results suggest a fundamental role for mechanosensing in mammalian development and illustrate that the mechanical environment should be taken into consideration when engineering implantable scaffolds or when producing therapeutically relevant cell populations in vitro.

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Last modified December 18, 2012

Open Access / Author retains copyright

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