机械敏感性离子通道,Piezo1响应于各种机械应力而诱导非选择性阳离子通量。然而,Piezo1激活产生的细胞的生物学解释和潜在机制仍然难以捉摸。这项研究使用新型的基于Förster共振能量转移(FRET)的生物传感器和单细胞成像分析,阐明了由通道激活和细胞行为驱动的Piezo1介导的Ca2流入。结果表明,细胞外Ca2+通过Piezo1流入需要完整的小窝蛋白,胆固醇,和细胞骨架支持。增加的细胞质Ca2+水平增强PKA,ERK,Rac1和ROCK活动,具有促进癌细胞存活和迁移的潜力。此外,我们证明Piezo1介导的Ca2流入上调膜皱褶,癌细胞转移的特征,利用时空图像相关光谱学。因此,我们的发现为Piezo1的功能提供了新的见解,表明Piezo1在癌细胞的行为中起着重要作用。
A mechanosensitive ion channel, Piezo1 induces non-selective cation flux in response to various mechanical stresses. However, the biological interpretation and underlying mechanisms of cells resulting from Piezo1 activation remain elusive. This study elucidates Piezo1-mediated Ca2+ influx driven by channel activation and cellular behavior using novel Förster Resonance Energy Transfer (FRET)-based biosensors and single-cell imaging analysis. Results reveal that extracellular Ca2+ influx via Piezo1 requires intact caveolin, cholesterol, and cytoskeletal support. Increased cytoplasmic Ca2+ levels enhance PKA, ERK, Rac1, and ROCK activity, which have the potential to promote cancer cell survival and migration. Furthermore, we demonstrate that Piezo1-mediated Ca2+ influx upregulates membrane ruffling, a characteristic feature of cancer cell metastasis, using spatiotemporal image correlation spectroscopy. Thus, our findings provide new insights into the function of Piezo1, suggesting that Piezo1 plays a significant role in the behavior of cancer cells.