StemBond hydrogels control the mechanical microenvironment for pluripotent stem cells
Tan, Bao Xiu
Agley, Chibeza C.
Winkel, Alexander K.
Stuart, Hannah T.
Nature Publishing Group UK
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Labouesse, C., Tan, B. X., Agley, C. C., Hofer, M., Winkel, A. K., Stirparo, G. G., Stuart, H. T., et al. (2021). StemBond hydrogels control the mechanical microenvironment for pluripotent stem cells. Nature Communications, 12 (1) https://doi.org/10.1038/s41467-021-26236-5
Funder: Medical Research Council (UK) Career Development Award (G1100312/1)
Funder: Medical Research Council (UK) MR/M011089/1 Wellcome Trust-Medical Research Council core funding to the Wellcome-MRC Cambridge Stem Cell Institute
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.
Article, /631/61/54/2295, /631/61/2320, /631/532/2117, /631/532/2435, /13, /14, /14/63, /13/100, /14/3, /38, /38/91, /14/19, /82/80, /38/88, article
Wellcome Trust (Wellcome) (PhD Grant)
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) (772426, 772798)
External DOI: https://doi.org/10.1038/s41467-021-26236-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329719