StemBond hydrogels control the mechanical microenvironment for pluripotent stem cells

Céline Labouesse, Bao Xiu Tan, Chibeza C. Agley, Moritz Hofer, Alexander K. Winkel, Giuliano G. Stirparo, Hannah T. Stuart, Christophe M. Verstreken, Carla Mulas, William Mansfield, Paul Bertone, Kristian Franze, José C. R. Silva () and Kevin J. Chalut ()
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Céline Labouesse: University of Cambridge
Bao Xiu Tan: University of Cambridge
Chibeza C. Agley: University of Cambridge
Moritz Hofer: University of Cambridge
Alexander K. Winkel: University of Cambridge
Giuliano G. Stirparo: University of Cambridge
Hannah T. Stuart: University of Cambridge
Christophe M. Verstreken: University of Cambridge
Carla Mulas: University of Cambridge
William Mansfield: University of Cambridge
Paul Bertone: University of Cambridge
Kristian Franze: University of Cambridge
José C. R. Silva: University of Cambridge
Kevin J. Chalut: University of Cambridge

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract Studies of mechanical signalling are typically performed by comparing cells cultured on soft and stiff hydrogel-based substrates. However, it is challenging to independently and robustly control both substrate stiffness and extracellular matrix tethering to substrates, making matrix tethering a potentially confounding variable in mechanical signalling investigations. Moreover, unstable matrix tethering can lead to poor cell attachment and weak engagement of cell adhesions. To address this, we developed StemBond hydrogels, a hydrogel in which matrix tethering is robust and can be varied independently of stiffness. We validate StemBond hydrogels by showing that they provide an optimal system for culturing mouse and human pluripotent stem cells. We further show how soft StemBond hydrogels modulate stem cell function, partly through stiffness-sensitive ERK signalling. Our findings underline how substrate mechanics impact mechanosensitive signalling pathways regulating self-renewal and differentiation, indicating that optimising the complete mechanical microenvironment will offer greater control over stem cell fate specification.

Date: 2021
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DOI: 10.1038/s41467-021-26236-5

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