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Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels

Hadden, W.J., Young, J.L., Holle, A.W., McFetridge, M.L., Kim, D.Y., Wijesinghe, P., Taylor-Weiner, H., Wen, J.H., Lee, A.R., Bieback, K. , Vo, B.-N., Sampson, David, Kennedy, B.F., Spatz, J.P., Engler, A.J. and Cho, Y.S. (2017) Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels Proceedings of the National Academy of Sciences of the United States of America, 114 (22). pp. 5647-5652.

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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.

Item Type: Article
Divisions : Faculty of Engineering and Physical Sciences
Faculty of Health and Medical Sciences
Authors :
NameEmailORCID
Hadden, W.J.
Young, J.L.
Holle, A.W.
McFetridge, M.L.
Kim, D.Y.
Wijesinghe, P.
Taylor-Weiner, H.
Wen, J.H.
Lee, A.R.
Bieback, K.
Vo, B.-N.
Sampson, Davidd.sampson@surrey.ac.uk
Kennedy, B.F.
Spatz, J.P.
Engler, A.J.
Cho, Y.S.
Date : 2017
DOI : 10.1073/pnas.1618239114
Uncontrolled Keywords : Extracellular matrix, Mechanobiology, Stem cell differentiation, Stem cell migration, Stiffness, acrylamide, collagen, fibronectin, lamin A, lamin B, MyoD1 protein, peroxisome proliferator activated receptor gamma, transcription factor, transcription factor mrtf a, transcription factor mrtf b, unclassified drug, acrylic acid resin, polyacrylamide gels, actin filament, actin polymerization, adipose derived stem cell, Article, atomic force microscopy, cell adhesion, cell differentiation, cell migration, cell proliferation, cell spreading, cross linking, elastography, human, human cell, hydrogel, immunofluorescence, intermediate filament, mechanotransduction, myoblast, optical coherence elastography, polymerization, priority journal, protein expression, protein function, rigidity, scanning electron microscopy, Young modulus, adult, cell culture technique, cell line, cell motion, chemistry, hydrogel, mechanotransduction, metabolism, physiology, procedures, stem cell, Acrylamide, Acrylic Resins, Adult, Cell Adhesion, Cell Culture Techniques, Cell Line, Cell Movement, Elastic Modulus, Humans, Hydrogels, Mechanotransduction, Cellular, Polymerization, Stem Cells
Depositing User : Maria Rodriguez-Marquez
Date Deposited : 04 Jun 2018 08:13
Last Modified : 19 Sep 2018 11:32
URI: http://epubs.surrey.ac.uk/id/eprint/846734

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