Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels

The spatial presentation of mechanical information is a key parameter for cell behavior. We have developed a method of polymerization control in which the differential diffusion distance of unreacted cross-linker and monomer into a prepolymerized hydrogel sink results in a tunable stiffness gradient...

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Hauptverfasser: Hadden, William J. (VerfasserIn) , Young, Jennifer (VerfasserIn) , Holle, Andrew W. (VerfasserIn) , Bieback, Karen (VerfasserIn) , Spatz, Joachim P. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 15 May 2017
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2017, Jahrgang: 114, Heft: 22, Pages: 5647-5652
ISSN:1091-6490
DOI:10.1073/pnas.1618239114
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1073/pnas.1618239114
Verlag, kostenfrei, Volltext: http://www.pnas.org/content/114/22/5647
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Verfasserangaben:William J. Hadden, Jennifer L. Young, Andrew W. Holle, Meg L. McFetridge, Du Yong Kim, Philip Wijesinghe, Hermes Taylor-Weiner, Jessica H. Wen, Andrew R. Lee, Karen Bieback, Ba-Ngu Vo, David D. Sampson, Brendan F. Kennedy, Joachim P. Spatz, Adam J. Engler, and Yu Suk Choi

MARC

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520 |a The spatial presentation of mechanical information is a key parameter for cell behavior. We have developed a method of polymerization control in which the differential diffusion distance of unreacted cross-linker and monomer into a prepolymerized hydrogel sink results in a tunable stiffness gradient at the cell-matrix interface. This simple, low-cost, robust method was used to produce polyacrylamide hydrogels with stiffness gradients of 0.5, 1.7, 2.9, 4.5, 6.8, and 8.2 kPa/mm, spanning the in vivo physiological and pathological mechanical landscape. Importantly, three of these gradients were found to be nondurotactic for human adipose-derived stem cells (hASCs), allowing the presentation of a continuous range of stiffnesses in a single well without the confounding effect of differential cell migration. Using these nondurotactic gradient gels, stiffness-dependent hASC morphology, migration, and differentiation were studied. Finally, the mechanosensitive proteins YAP, Lamin A/C, Lamin B, MRTF-A, and MRTF-B were analyzed on these gradients, providing higher-resolution data on stiffness-dependent expression and localization. 
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