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StemBond hydrogels control the mechanical microenvironment for pluripotent stem cells.

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cam.issuedOnline2021-10-21
dc.contributor.authorLabouesse, Céline
dc.contributor.authorTan, Bao Xiu
dc.contributor.authorAgley, Chibeza C
dc.contributor.authorHofer, Moritz
dc.contributor.authorWinkel, Alexander K
dc.contributor.authorStirparo, Giuliano G
dc.contributor.authorStuart, Hannah T
dc.contributor.authorVerstreken, Christophe M
dc.contributor.authorMulas, Carla
dc.contributor.authorMansfield, William
dc.contributor.authorBertone, Paul
dc.contributor.authorFranze, Kristian
dc.contributor.authorSilva, José CR
dc.contributor.authorChalut, Kevin J
dc.contributor.orcidLabouesse, Céline [0000-0002-9791-898X]
dc.contributor.orcidHofer, Moritz [0000-0002-9714-0143]
dc.contributor.orcidStirparo, Giuliano G [0000-0002-5911-8682]
dc.contributor.orcidVerstreken, Christophe M [0000-0001-9038-1094]
dc.contributor.orcidMulas, Carla [0000-0002-9492-6482]
dc.contributor.orcidFranze, Kristian [0000-0002-8425-7297]
dc.contributor.orcidSilva, José CR [0000-0001-5487-1117]
dc.contributor.orcidChalut, Kevin J [0000-0001-6200-9690]
dc.date.accessioned2021-12-15T10:09:50Z
dc.date.available2021-12-15T10:09:50Z
dc.date.issued2021-10-21
dc.date.updated2021-12-15T10:09:49Z
dc.description.abstractStudies 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.
dc.identifier.doi10.17863/CAM.78909
dc.identifier.eissn2041-1723
dc.identifier.issn2041-1723
dc.identifier.otherPMC8531294
dc.identifier.other34675200
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331455
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41467-021-26236-5
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2041-1723
dc.sourcenlmid: 101528555
dc.subjectAnimals
dc.subjectBiomechanical Phenomena
dc.subjectCell Adhesion
dc.subjectCell Culture Techniques
dc.subjectCell Differentiation
dc.subjectCells, Cultured
dc.subjectExtracellular Matrix
dc.subjectHumans
dc.subjectHydrogels
dc.subjectMechanotransduction, Cellular
dc.subjectMice
dc.subjectPluripotent Stem Cells
dc.titleStemBond hydrogels control the mechanical microenvironment for pluripotent stem cells.
dc.typeArticle
dcterms.dateAccepted2021-09-22
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume12
pubs.funder-project-idMedical Research Council (G1100312)
pubs.funder-project-idWellcome Trust (101861/Z/13/Z)
pubs.funder-project-idMedical Research Council (MR/M011089/1)
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
pubs.funder-project-idEuropean Research Council (772798)
pubs.funder-project-idEuropean Research Council (772426)
pubs.funder-project-idMedical Research Council (MC_PC_17230)
pubs.funder-project-idMedical Research Council (MR/R017735/1)
pubs.funder-project-idMedical Research Council (MR/R015635/1)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/R018588/1)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-021-26236-5

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