Graphene oxide (GO), with good hydrophilicity and biocompatibility, is widely explored as a carrier for various factors in the field of stem cell differentiation . However, its function of sustaining the stemness of mouse embryonic stem cells (mESCs) and the underlying mechanisms of this process remains undiscovered. Herein, we explored the biofunction of GO on mESCs and revealed the involved signaling pathways and key gene. The alkaline phosphatase activity detection, pluripotency genes quantification and the teratomas formation in vivo confirmed that GO nanosheets could sustain the self-renewal ability of mESCs instead of influencing its pluripotency . The underlying signaling pathways were uncovered by RNA-seq that integrin signaling pathway was involved in the biofunction of GO on mESCs and Vinculin turned to be a key gene for the effect of GO. Further experiments confirmed that the downregulation of Vinculin influenced the fate of mESCs through decreasing the expression of MEK1. Altogether, the study demonstrated for the first time that GOs hold the potential in sustaining the self-renewal of mESCs and clarified the mechanism of this function, which make it play a new role in stem cell research and regenerative medicine .
Zijia Chen,Xiaoning Han,Bo Che,Huiping Feng,Yue Zhou,Linhong Deng,Xiang Wang
Soft tissues experience strain under mechanical stresses, storing energy as residual stresses and strain energy. However, the specific impact of such strain on cell migration and its molecular mechanisms remains unclear. In this study, we investigated this by using polydimethylsiloxane (PDMS) membranes with varying prestrain levels but constant stiffness to mimic tissue-like conditions. Results showed that higher prestrain levels enhanced 3T3 fibroblast adhesion and reduced filopodia formation. Elevated prestrain also increased integrin and vinculin expression, which was associated with lower cell migration rates. Notably, both 3T3 fibroblasts and primary rat airway smooth muscle cells migrated faster toward higher prestrain areas on substrates with strain gradients. Knockdown of integrin or vinculin inhibited 3T3 cell migration directionality, highlighting their critical role. This research reveals a mechanobiological pathway where strain gradients direct cell migration, providing insight into a common mechanotransduction pathway influencing cellular responses to both stiffness and strain-related mechanical cues.
Jiao Yongjie,Li Xiaojing,Chen Jinjie,Li Chaojing,Liu Laijun,Liu Xingxing,Wang Fujun,Chen Guang,Wang Lu
Fibrosis is a common problem in soft tissue regeneration, often caused by the differentiation of fibroblasts into myofibroblasts. Because of the nanoscale topology that regulates the mechanical transduction of cells, nanofibers or nanoparticles are commonly used to modulate fibroblast differentiation. However, the strength of nanofibers is insufficient, and the physiological toxicity of nanoparticles still remains to be verified. In this study, self-induced crystallization was used to construct nano-protrusions on the random and aligned polycaprolactone microfibers to regulate the behavior of fibroblasts. The results revealed that the mechanical properties of microfibers with a nanoscale topology were improved. Immunofluorescence staining manifested that nano-protrusions impeded the activation of integrins and vinculins, thereby inhibiting the nuclear transfer of Yes-associated protein, resulting in a decrease in the expression of α- smooth muscle actin. Nanoscale topology of microfibers hampered the activation of the Rho/ROCK signalling pathway. In general, we used a simple process to construct a fibrous scaffold with a micro-nano multilevel structure. This structure can hinder the transformation of fibroblasts into myofibroblasts on both random and aligned fibers, which is expected to prevent fibrosis. Graphical abstract
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