Stem Cell Mechanosensation on Gelatin Methacryloyl (GelMA) Stiffness Gradient Hydrogels
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Annals of Biomedical Engineering ( 2019) https://doi.org/10.1007/s10439-019-02428-5
Original Article
Stem Cell Mechanosensation on Gelatin Methacryloyl (GelMA) Stiffness Gradient Hydrogels CLAIRE KIM,1 JENNIFER L. YOUNG,2,3 ANDREW W. HOLLE,2,3 KWANGHEE JEONG,4 LUKE G. MAJOR,1 JI HOON JEONG,5 ZACHARY M. AMAN,4 DONG-WOOK HAN,6 YONGSUNG HWANG,5 JOACHIM P. SPATZ,2,3 and YU SUK CHOI 1 1 School of Human Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia; Department of Cellular Biophysics, Max Planck Institute for Medical Research, 69120 Heidelberg, Germany; 3Department of Biophysical Chemistry, University of Heidelberg, 69117 Heidelberg, Germany; 4Fluid Science and Resources, Department of Chemical Engineering, School of Engineering, University of Western Australia, Perth, WA 6009, Australia; 5Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan-si, Chungcheongnam-do 31151, Korea; and 6Department of CognoMechatronics Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Busan 46241, Korea 2
(Received 26 September 2019; accepted 27 November 2019) Associate Editor Kent Leach oversaw the review of this article.
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. Keywords—Mechanosensitive, Stiffness, Gradient, Stem cell, Differentiation.
Address correspondence to Yu Suk Choi, School of Human Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia. Electronic mail: [email protected]
INTRODUCTION The microenvironment surrounding stem cells is known to impose a wide variety of chemical and mechanical cues t
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