Stem Cell Mechanosensation on Gelatin Methacryloyl (GelMA) Stiffness Gradient Hydrogels.
Ann Biomed Eng
; 48(2): 893-902, 2020 Feb.
Article
em En
| MEDLINE
| ID: mdl-31802282
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
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Antígenos de Diferenciação
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Tecido Adiposo
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Regulação da Expressão Gênica
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Hidrogéis
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Mecanotransdução Celular
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Gelatina
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article