Anchoring points determine fate of stem cells

Mesenchymal Stem Cells (hMSCs) cultured on a Polyacrylamide gel for 7 days: Cells stained in blue are ALP positive which is a marker for osteogenic differentiation, while the cells that contain red oil droplets underwent adipogenic differentiation. Credit: Bojun Li and Prof. Viola Vogel / ETH Zurich

(Phys.org) -- Researchers were positive: a substrates softness influences the behaviour of stem cells in culture. Now other researchers have made a new discovery: the number of anchoring points to which the cells can adhere is pivotal.

How stem cells differentiate is evidently not so much a question of the stiffness of the substrate upon which they thrive, as the cells mechanical anchoring on the substrate surface. This is shown in a study recently published in Nature Materials by researchers from various European universities, including ETH Zurich.

Since 2006 the research community has been convinced that stem cells can feel the softness of materials they grow upon. Scientists mainly drew this conclusion from correlations between the softness of the substrate and the cells behavior.

The new research project, to which ETH-Zurich professor Viola Vogel and her doctoral student Bojun Li made a key contribution, has come to another conclusion. It reveals that the properties of the network structure of polymers are instrumental in regulating the anchoring of the collagen proteins to which the cells ultimately adhere. And these anchors influence the differentiation of stem cells.

Good protein adhesion makes surface seem stiff

In a series of experiments, which Britta Trappmann from Cambridge University partly conducted at ETH Zurich, the cells were applied to two different polymers of the same softness. However, the polymers differed in terms of their surface structure, which regulates the number of firmly anchored collagen proteins.

If the researchers reduced the number of well-anchored proteins on a hard surface, the cells behaved in the same way as on a soft base. If the anchors were close together, the stem cells differentiated into bone cells. If the anchors were further apart, they became fat cells. The simple correlation that a materials stiffness or elasticity can govern the differentiation of stem cells is therefore not universally valid, says Vogel.

Paradigm shift in cultivation of stem cells

With their experiment, the researchers shake a paradigm. In a study conducted in 2006, scientists revealed a connection between polymer stiffness and the degree of cell differentiation. However, the researchers varied the stiffness of the polymer by varying its network structure.

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Anchoring points determine fate of stem cells