Cell mechanics has been shown to regulate stem cell differentiation. We have previously reported that altered cell stiffness of mesenchymal stem cells can delay or facilitate biochemically directed differentiation. One of the factors that can affect the cell stiffness is cholesterol. However, the effect of cholesterol on differentiation of human mesenchymal stem cells remains elusive. In this paper, we demonstrate that cholesterol is involved in the modulation of the cell stiffness and subsequent adipogenic differentiation. Rapid cytoskeletal actin reorganization was evident and correlated with the cell's Young's modulus measured using atomic force microscopy. In addition, the level of membrane-bound cholesterol was found to increase during adipogenic differentiation and inversely varied with the cell stiffness. Furthermore, cholesterol played a key role in the regulation of the cell morphology and biomechanics, suggesting its crucial involvement in mechanotransduction. To better understand the underlying mechanisms, we investigated the effect of cholesterol on the membrane–cytoskeleton linker proteins (ezrin and moesin). Cholesterol depletion was found to upregulate the ezrin expression which promoted cell spreading, increased Young's modulus, and hindered adipogenesis. In contrast, cholesterol enrichment increased the moesin expression, decreased Young's modulus, and induced cell rounding and facilitated adipogenesis. Taken together, cholesterol appears to regulate the stem cell mechanics and adipogenesis through the membrane-associated linker proteins.
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August 2019
Research-Article
Cholesterol-Dependent Modulation of Stem Cell Biomechanics: Application to Adipogenesis
Shan Sun,
Shan Sun
Department of Bioengineering,
University of Illinois at Chicago,
Chicago, IL 60607
e-mail: shansun88@gmail.com
University of Illinois at Chicago,
Chicago, IL 60607
e-mail: shansun88@gmail.com
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Djanybek Adyshev,
Djanybek Adyshev
Department of Medicine,
University of Illinois at Chicago,
Chicago, IL 60607
e-mail: dadyshev@gmail.com
University of Illinois at Chicago,
Chicago, IL 60607
e-mail: dadyshev@gmail.com
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Amit Paul,
Amit Paul
Department of Bioengineering,
University of Illinois at Chicago,
Chicago, IL 60607
e-mail: amitpaul88@gmail.com
University of Illinois at Chicago,
Chicago, IL 60607
e-mail: amitpaul88@gmail.com
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Andrew McColloch,
Andrew McColloch
Department of Bioengineering,
University of Texas at Arlington,
Arlington, TX 76019
e-mail: andrew.mccolloch@mavs.uta.edu
University of Texas at Arlington,
Arlington, TX 76019
e-mail: andrew.mccolloch@mavs.uta.edu
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Michael Cho
Michael Cho
Department of Bioengineering,
University of Texas at Arlington,
Arlington, TX 76019
e-mail: michael.cho@uta.edu
University of Texas at Arlington,
Arlington, TX 76019
e-mail: michael.cho@uta.edu
1Corresponding author.
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Shan Sun
Department of Bioengineering,
University of Illinois at Chicago,
Chicago, IL 60607
e-mail: shansun88@gmail.com
University of Illinois at Chicago,
Chicago, IL 60607
e-mail: shansun88@gmail.com
Djanybek Adyshev
Department of Medicine,
University of Illinois at Chicago,
Chicago, IL 60607
e-mail: dadyshev@gmail.com
University of Illinois at Chicago,
Chicago, IL 60607
e-mail: dadyshev@gmail.com
Steven Dudek
Amit Paul
Department of Bioengineering,
University of Illinois at Chicago,
Chicago, IL 60607
e-mail: amitpaul88@gmail.com
University of Illinois at Chicago,
Chicago, IL 60607
e-mail: amitpaul88@gmail.com
Andrew McColloch
Department of Bioengineering,
University of Texas at Arlington,
Arlington, TX 76019
e-mail: andrew.mccolloch@mavs.uta.edu
University of Texas at Arlington,
Arlington, TX 76019
e-mail: andrew.mccolloch@mavs.uta.edu
Michael Cho
Department of Bioengineering,
University of Texas at Arlington,
Arlington, TX 76019
e-mail: michael.cho@uta.edu
University of Texas at Arlington,
Arlington, TX 76019
e-mail: michael.cho@uta.edu
1Corresponding author.
Manuscript received August 17, 2018; final manuscript received March 13, 2019; published online May 6, 2019. Assoc. Editor: Nathan Sniadecki.
J Biomech Eng. Aug 2019, 141(8): 081005 (10 pages)
Published Online: May 6, 2019
Article history
Received:
August 17, 2018
Revised:
March 13, 2019
Citation
Sun, S., Adyshev, D., Dudek, S., Paul, A., McColloch, A., and Cho, M. (May 6, 2019). "Cholesterol-Dependent Modulation of Stem Cell Biomechanics: Application to Adipogenesis." ASME. J Biomech Eng. August 2019; 141(8): 081005. https://doi.org/10.1115/1.4043253
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