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  Stem cell mechanosensation on gelatin methacryloyl (GelMA) stiffness gradient hydrogels

Kim, C., Young, J. L., Holle, A. W., Jeong, K., Major, L. G., Jeong, J. H., et al. (2020). Stem cell mechanosensation on gelatin methacryloyl (GelMA) stiffness gradient hydrogels. Annals of biomedical engineering, 48(2), 893-902. doi:10.1007/s10439-019-02428-5.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-5856-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-F7AD-2
Genre: Journal Article

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AnnBiomedEngineer_48_2020_893.pdf (Any fulltext), 3MB
 
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 Creators:
Kim, Claire, Author
Young, Jennifer L.1, 2, Author              
Holle, Andrew W.1, 2, Author              
Jeong, Kwanghee, Author
Major, Luke G., Author
Jeong, Ji Hoon, Author
Aman, Zachary M., Author
Han, Dong-Wook, Author
Hwang, Yongsung, Author
Spatz, Joachim P.1, 2, Author              
Choi, Yu Suk, Author
Affiliations:
1Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_2364731              
2Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany, ou_persistent22              

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Free keywords: Mechanosensitive; Stiffness; Gradient; Stem cell; Differentiation
 Abstract: Stiffness gradient hydrogels are a useful platform for studying mechanical interactions between cells and their surrounding environments. Here, we developed linear stiffness gradient hydrogels by controlling the polymerization of gelatin methacryloyl (GelMA) via differential UV penetration with a gradient photomask. Based on previous observations, a stiffness gradient GelMA hydrogel was created ranging from ~ 4 to 13 kPa over 15 mm (0.68 kPa/mm), covering the range of physiological tissue stiffness from fat to muscle, thereby allowing us to study stem cell mechanosensation and differentiation. Adipose-derived stem cells on these gradient hydrogels showed no durotaxis, which allowed for the screening of mechanomarker expression without confounding directed migration effects. In terms of morphological markers, the cell aspect ratio showed a clear positive correlation to the underlying substrate stiffness, while no significant correlation was found in cell size, nuclear size, or nuclear aspect ratio. Conversely, expression of mechanomarkers (i.e., Lamin A, YAP, and MRTFa) all showed a highly significant correlation to stiffness, which could be disrupted via inhibition of non-muscle myosin or Rho/ROCK signalling. Furthermore, we showed that cells plated on stiffer regions became stiffer themselves, and that stem cells showed stiffness-dependent differentiation to fat or muscle as has been previously reported in the literature.

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Language(s): eng - English
 Dates: 2019-09-262019-09-272019-12-042020-02-01
 Publication Status: Published in print
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1007/s10439-019-02428-5
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Title: Annals of biomedical engineering
Source Genre: Journal
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Publ. Info: US : Springer
Pages: - Volume / Issue: 48 (2) Sequence Number: - Start / End Page: 893 - 902 Identifier: ISSN: 0090-6964
ISSN: 1573-9686