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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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
15 May 2017
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| In: |
Proceedings of the National Academy of Sciences of the United States of America
Year: 2017, Volume: 114, Issue: 22, Pages: 5647-5652 |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.1618239114 |
| Online Access: | 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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| Author Notes: | 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 |
| Summary: | 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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| Item Description: | Gesehen am 12.09.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.1618239114 |