StemBond hydrogels control the mechanical microenvironment for pluripotent stem cells.


Type
Article
Change log
Authors
Tan, Bao Xiu 
Agley, Chibeza C 
Winkel, Alexander K 
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.

Description
Keywords
Animals, Biomechanical Phenomena, Cell Adhesion, Cell Culture Techniques, Cell Differentiation, Cells, Cultured, Extracellular Matrix, Humans, Hydrogels, Mechanotransduction, Cellular, Mice, Pluripotent Stem Cells
Journal Title
Nat Commun
Conference Name
Journal ISSN
2041-1723
2041-1723
Volume Title
12
Publisher
Springer Science and Business Media LLC
Sponsorship
Medical Research Council (G1100312)
Wellcome Trust (101861/Z/13/Z)
Medical Research Council (MR/M011089/1)
Wellcome Trust (203151/Z/16/Z)
European Research Council (772798)
European Research Council (772426)
Medical Research Council (MC_PC_17230)
Medical Research Council (MR/R017735/1)
Medical Research Council (MR/R015635/1)
Biotechnology and Biological Sciences Research Council (BB/R018588/1)