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    Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels

    Access Status
    Open access via publisher
    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.
    Date
    2017
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Hadden, W. and Young, J. and Holle, A. and McFetridge, M. and Kim, D.Y. and Wijesinghe, P. and Taylor-Weiner, H. et al. 2017. Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels. Proceedings of the National Academy of Sciences of USA. 114 (22): pp. 5647-5652.
    Source Title
    Proceedings of the National Academy of Sciences of USA
    DOI
    10.1073/pnas.1618239114
    ISSN
    0027-8424
    School
    Department of Electrical and Computer Engineering
    URI
    http://hdl.handle.net/20.500.11937/56114
    Collection
    • Curtin Research Publications
    Abstract

    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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