Molecular Mobility of Polyrotaxane Surfaces Alleviates Oxidative Stress-Induced Senescence in Mesenchymal Stem Cells

Polyrotaxane is a supramolecular assembly consisting of multiple cyclic molecules threaded by a linear polymer. One of the unique properties of polyrotaxane is molecular mobility, cyclic molecules moving along the linear polymer. Molecular mobility of polyrotaxane surfaces affects cell spreading, differentiation, and other cell-related aspects through changing subcellular localization of yes-associated proteins (YAPs). Subcellular YAP localization is also related to cell senescence derived from oxidative stress, which is known to cause cancer, diabetes, and heart disease. Herein, the effects of polyrotaxane surface molecular mobility on subcellular YAP localization and cell senescence following H₂O₂-induced oxidative stress are evaluated in human mesenchymal stem cells (HMSCs) cultured on polyrotaxane surfaces with different molecular mobilities. Oxidative stress promotes cytoplasmic YAP localization in HMSCs on high-mobility polyrotaxane surfaces; however, low-mobility polyrotaxane surfaces more effectively maintain nuclear YAP localization, exhibiting lower senescence-associated β-galactosidase activity and senescence-related gene expression and DNA damage than that seen with the high-mobility surfaces. These results suggest that the molecular mobility of polyrotaxane surfaces regulates subcellular YAP localization, thereby protecting HMSCs from oxidative stress-induced cell senescence. Applying the molecular mobility of polyrotaxane surfaces to implantable scaffolds can provide insights into the prevention and treatment of diseases caused by oxidative stress.