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  Volume adaptation controls stem cell mechanotransduction

Major, L. G., Holle, A. W., Young, J. L., Hepburn, M. S., Jeong, K., Chin, I. L., et al. (2019). Volume adaptation controls stem cell mechanotransduction. ACS Applied Materials and Interfaces, 11(49), 45520-45530. doi:10.1021/acsami.9b19770.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-3B77-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-5EFB-8
Genre: Journal Article

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 Creators:
Major, Luke G, Author
Holle, Andrew W.1, 2, Author              
Young, Jennifer L.1, 2, Author              
Hepburn, Matt S, Author
Jeong, Kwanghee, Author
Chin, Ian L, Author
Sanderson, Rowan W, Author
Jeong, Ji Hoon, Author
Aman, Zachary M., Author
Kennedy, Brendan F, Author
Hwang, Yongsung, Author
Han, Dong-Wook, Author
Park, Hyun Woo, Author
Guan, Kun-Liang, 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: cellular volume, stiffness gradient, mechanotransduction, stem cell differentiation, extracellular matrix, mechanobiology
 Abstract: Recent studies have found discordant mechanosensitive outcomes when comparing 2D and 3D, highlighting the need for tools to study mechanotransduction in 3D across a wide spectrum of stiffness. A gelatin methacryloyl (GelMA) hydrogel with a continuous stiffness gradient ranging from 5 to 38 kPa was developed to recapitulate physiological stiffness conditions. Adipose-derived stem cells (ASCs) were encapsulated in this hydrogel, and their morphological characteristics and expression of both mechanosensitive proteins (Lamin A, YAP, and MRTFa) and differentiation markers (PPARγ and RUNX2) were analyzed. Low-stiffness regions (∼8 kPa) permitted increased cellular and nuclear volume and enhanced mechanosensitive protein localization in the nucleus. This trend was reversed in high stiffness regions (∼30 kPa), where decreased cellular and nuclear volumes and reduced mechanosensitive protein nuclear localization were observed. Interestingly, cells in soft regions exhibited enhanced osteogenic RUNX2 expression, while those in stiff regions upregulated the adipogenic regulator PPARγ, suggesting that volume, not substrate stiffness, is sufficient to drive 3D stem cell differentiation. Inhibition of myosin II (Blebbistatin) and ROCK (Y-27632), both key drivers of actomyosin contractility, resulted in reduced cell volume, especially in low-stiffness regions, causing a decorrelation between volume expansion and mechanosensitive protein localization. Constitutively active and inactive forms of the canonical downstream mechanotransduction effector TAZ were stably transfected into ASCs. Activated TAZ resulted in higher cellular volume despite increasing stiffness and a consistent, stiffness-independent translocation of YAP and MRTFa into the nucleus. Thus, volume adaptation as a function of 3D matrix stiffness can control stem cell mechanotransduction and differentiation.

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Language(s): eng - English
 Dates: 2019-11-012019-11-122019-11-122019-11-12
 Publication Status: Published in print
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Degree: -

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Title: ACS Applied Materials and Interfaces
  Abbreviation : ACS Appl. Mater. Interfaces
Source Genre: Journal
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Publ. Info: Washington, DC : American Chemical Society
Pages: - Volume / Issue: 11 (49) Sequence Number: - Start / End Page: 45520 - 45530 Identifier: ISSN: 1944-8244
CoNE: https://pure.mpg.de/cone/journals/resource/1944-8244