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: Hadden, W., Young, J., Holle, A., McFetridge, M., Kim, Du Yong, Wijesinghe, P., Taylor-Weiner, H., Wen, J., Lee, A., Bieback, K., Vo, Ba-Ngu, Sampson, D., Kennedy, B., Spatz, J., Engler, A., Cho, Y.
Format: Journal Article
Published: National Academy of Sciences 2017
Online Access:http://hdl.handle.net/20.500.11937/56114
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author Hadden, W.
Young, J.
Holle, A.
McFetridge, M.
Kim, Du Yong
Wijesinghe, P.
Taylor-Weiner, H.
Wen, J.
Lee, A.
Bieback, K.
Vo, Ba-Ngu
Sampson, D.
Kennedy, B.
Spatz, J.
Engler, A.
Cho, Y.
author_facet Hadden, W.
Young, J.
Holle, A.
McFetridge, M.
Kim, Du Yong
Wijesinghe, P.
Taylor-Weiner, H.
Wen, J.
Lee, A.
Bieback, K.
Vo, Ba-Ngu
Sampson, D.
Kennedy, B.
Spatz, J.
Engler, A.
Cho, Y.
author_sort Hadden, W.
building Curtin Institutional Repository
collection Online Access
description 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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format Journal Article
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institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T10:05:28Z
publishDate 2017
publisher National Academy of Sciences
recordtype eprints
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spelling curtin-20.500.11937-561142023-02-22T06:24:22Z Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels Hadden, W. Young, J. Holle, A. McFetridge, M. Kim, Du Yong Wijesinghe, P. Taylor-Weiner, H. Wen, J. Lee, A. Bieback, K. Vo, Ba-Ngu Sampson, D. Kennedy, B. Spatz, J. Engler, A. Cho, Y. 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/56114 10.1073/pnas.1618239114 National Academy of Sciences unknown
spellingShingle Hadden, W.
Young, J.
Holle, A.
McFetridge, M.
Kim, Du Yong
Wijesinghe, P.
Taylor-Weiner, H.
Wen, J.
Lee, A.
Bieback, K.
Vo, Ba-Ngu
Sampson, D.
Kennedy, B.
Spatz, J.
Engler, A.
Cho, Y.
Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels
title Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels
title_full Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels
title_fullStr Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels
title_full_unstemmed Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels
title_short Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels
title_sort stem cell migration and mechanotransduction on linear stiffness gradient hydrogels
url http://hdl.handle.net/20.500.11937/56114