Sun Yanli, Zhao Hucheng
Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, School of Aerospace Engineering, Tsinghua University, Beijing, 100084, China; School of Mechanical Engineering, Xinjiang University, Urumqi, 830046, China.
Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, School of Aerospace Engineering, Tsinghua University, Beijing, 100084, China.
Biochem Biophys Res Commun. 2025 Aug 30;776:152186. doi: 10.1016/j.bbrc.2025.152186. Epub 2025 Jun 14.
Intercellular communication and cellular material exchange are essential for the development, tissue repair, and survival of multicellular organisms. Tunneling nanotubes (TNTs) serve as long-distance intercellular connections that facilitate the transmission of biochemical and electrical signals between cells. However, the mechanisms underlying this process remain largely unknown. This study uses mechanical stimulation to explore the transmission and mechanisms of mechano-electrical signals mediated by TNTs. We assessed both gap junction (GJ)-mediated and TNT-mediated intercellular electrical coupling in HEK cells, A549 cells, and C2C12 cells. Our results show that the coupling ratio was lower in HEK cells compared to A549 cells, with the highest ratio observed in C2C12 cells. Additionally, the strength of TNT-mediated electrical coupling decreased as TNT length increased. Using C2C12 cells as a model, we found that Ca influx and the gap junction protein Connexin 43 (Cx43) play roles in TNT-mediated electrical coupling induced by mechanical stimulation. Mechanical stimulation triggers extracellular Ca entry into C2C12 cells via mechanosensitive and T-type calcium channels. Our experiments also demonstrate that TNT-mediated electrical coupling between C2C12 cells is predominantly unidirectional. These findings provide new insights into the mechanisms of intercellular electrical signal transmission.
细胞间通讯和细胞物质交换对于多细胞生物的发育、组织修复及生存至关重要。隧道纳米管（TNTs）作为长距离细胞间连接，促进细胞间生化和电信号的传递。然而，这一过程背后的机制仍 largely 未知。本研究利用机械刺激来探索由 TNTs 介导的机电信号的传递及机制。我们评估了 HEK 细胞、A549 细胞和 C2C12 细胞中缝隙连接（GJ）介导的和 TNT 介导的细胞间电偶联。我们的结果表明，与 A549 细胞相比，HEK 细胞中的偶联率较低，在 C2C12 细胞中观察到的偶联率最高。此外，TNT 介导的电偶联强度随着 TNT 长度的增加而降低。以 C2C12 细胞为模型，我们发现钙离子内流和缝隙连接蛋白连接蛋白 43（Cx43）在机械刺激诱导的 TNT 介导的电偶联中发挥作用。机械刺激通过机械敏感和 T 型钙通道触发细胞外钙离子进入 C2C12 细胞。我们的实验还表明，C2C12 细胞之间 TNT 介导的电偶联主要是单向的。这些发现为细胞间电信号传递机制提供了新的见解。
