Dataset Information

A biomimetic gelatin-based platform elicits a pro-differentiation effect on podocytes through mechanotransduction.

ABSTRACT: Using a gelatin microbial transglutaminase (gelatin-mTG) cell culture platform tuned to exhibit stiffness spanning that of healthy and diseased glomeruli, we demonstrate that kidney podocytes show marked stiffness sensitivity. Podocyte-specific markers that are critical in the formation of the renal filtration barrier are found to be regulated in association with stiffness-mediated cellular behaviors. While podocytes typically de-differentiate in culture and show diminished physiological function in nephropathies characterized by altered tissue stiffness, we show that gelatin-mTG substrates with Young's modulus near that of healthy glomeruli elicit a pro-differentiation and maturation response in podocytes better than substrates either softer or stiffer. The pro-differentiation phenotype is characterized by upregulation of gene and protein expression associated with podocyte function, which is observed for podocytes cultured on gelatin-mTG gels of physiological stiffness independent of extracellular matrix coating type and density. Signaling pathways involved in stiffness-mediated podocyte behaviors are identified, revealing the interdependence of podocyte mechanotransduction and maintenance of their physiological function. This study also highlights the utility of the gelatin-mTG platform as an in vitro system with tunable stiffness over a range relevant for recapitulating mechanical properties of soft tissues, suggesting its potential impact on a wide range of research in cellular biophysics.

SUBMITTER: Hu M

PROVIDER: S-EPMC5338254 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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A biomimetic gelatin-based platform elicits a pro-differentiation effect on podocytes through mechanotransduction.

Hu Mufeng M Azeloglu Evren U EU Ron Amit A Tran-Ba Khanh-Hoa KH Calizo Rhodora C RC Tavassoly Iman I Bhattacharya Smiti S Jayaraman Gomathi G Chen Yibang Y Rabinovich Vera V Iyengar Ravi R Hone James C JC He John C JC Kaufman Laura J LJ

Scientific reports 20170306

Using a gelatin microbial transglutaminase (gelatin-mTG) cell culture platform tuned to exhibit stiffness spanning that of healthy and diseased glomeruli, we demonstrate that kidney podocytes show marked stiffness sensitivity. Podocyte-specific markers that are critical in the formation of the renal filtration barrier are found to be regulated in association with stiffness-mediated cellular behaviors. While podocytes typically de-differentiate in culture and show diminished physiological functio ...[more]

PMID: 28262745

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Project description:The mechanical behavior of soft tissue extracellular matrix is time dependent. Moreover, it evolves over time due to physiological processes as well as aging and disease. Measuring and quantifying the time-dependent mechanical behavior of soft tissues and materials pose a challenge, not only because of their labile and hydrated nature but also because of the lack of a common definition of terms and understanding of models for characterizing viscoelasticity. Here, we review the most important measurement techniques and models used to determine the viscoelastic properties of soft hydrated materials-or hydrogels-underlining the difference between viscoelastic behavior and the properties and descriptors used to quantify viscoelasticity. We then discuss the principal factors, which determine tissue viscoelasticity in vivo and summarize what we currently know about cell response to time-dependent materials, outlining fundamental factors that have to be considered when interpreting results. Particular attention is given to the relationship between the different time scales involved (mechanical, cellular and observation time scales), as well as scaling principles, all of which must be considered when designing viscoelastic materials and performing experiments for biomechanics or mechanobiology applications. From this overview, key considerations and directions for furthering insights and applications in the emergent field of cell viscoelastic mechanotransduction are provided. Impact statement Our tissues are viscoelastic: they respond to mechanical stresses and strains in a time-dependent manner. Their mechanical behavior also evolves over time due to growth, aging, remodeling and disease. Understanding cell response to time-dependent and time-evolving mechanical cues is important for a better comprehension of a wide number of pathophysiological processes and for the design of biomimetic substrates, which can be used as physiologically relevant in vitro models and in regenerative medicine applications. This review highlights the importance of a more rigorous approach toward viscoelastic material design and testing for cell mechanobiology studies, which embrace the entire spectrum of elasto- and viscotransduction.

Dataset Information

A biomimetic gelatin-based platform elicits a pro-differentiation effect on podocytes through mechanotransduction.

Publications

A biomimetic gelatin-based platform elicits a pro-differentiation effect on podocytes through mechanotransduction.

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