Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels

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, Yu Suk Cho*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

211 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5647-5652
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number22
Early online date15 May 2017
DOIs
Publication statusPublished - 30 May 2017

Keywords

  • Mechanobiology
  • Stem cell migration
  • Stem cell differentiation
  • Extracellular matrix
  • Stiffness

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