Förster Resonance Energy Transfer-Based Single-Cell Imaging Reveals Piezo1-Induced Ca2+ Flux Mediates Membrane Ruffling and Cell Survival

• DOI: 10.3389/fcell.2022.865056
• Publication Date: 2022-05-13T07:17:12Z
• Authors: Heon-Su Kim; Jung-Soo Suh; Yoon-Kwan Jang; Sang-Hyun Ahn; Gyu-Ho Choi; Jin-Young Yang; Gah-Hyun Lim; Youngmi Jung; Jie Jiang; Jie Sun; Myungeun Suk; Yingxiao Wang; Tae-Jin Kim
• Keywords: 0301 basic medicine; Cell and Developmental Biology; 03 medical and health sciences; calcium; QH301-705.5; FRET; membrane ruffling; Piezo1; Biology (General); biosensors; 3. Good health

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.