Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels

Hadden, W, Young, J, Holle, A, McFetridge, M and Kim, D 2017, 'Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 22, pp. 5647-5652.


Document type: Journal Article
Collection: Journal Articles

Title Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels
Author(s) Hadden, W
Young, J
Holle, A
McFetridge, M
Kim, D
Year 2017
Journal name Proceedings of the National Academy of Sciences of the United States of America
Volume number 114
Issue number 22
Start page 5647
End page 5652
Total pages 6
Publisher National Academy of Sciences
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.
Subject Biomaterials
Keyword(s) Extracellular matrix
Mechanobiology
Stem cell differentiation
Stem cell migration
Stiffness
DOI - identifier 10.1073/pnas.1618239114
Copyright notice © 2018 National Academy of Sciences.
ISSN 0027-8424
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