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

作者：Hu Mufeng; Azeloglu Evren U; Ron Amit; Khanh Hoa Tran Ba; Calizo Rhodora C; Tavassoly Iman; Bhattacharya Smiti; Jayaraman Gomathi; Chen Yibang; Rabinovich Vera; Iyengar Ravi; Hone James C; He John C^*; Kaufman Laura J^*

来源：Scientific Reports, 2017, 7(1): 43934.

DOI：10.1038/srep43934

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.

• 出版日期2017-3-6