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由不同机制形成的细胞间隧道纳米管的力学性能。

Mechanical properties of intercellular tunneling nanotubes formed by different mechanisms.

作者信息

Sun Yanli, Zhang Huikai, Zavodnik Ilya B, Zhao Hucheng, Feng Xiqiao

机构信息

Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, School of Aerospace Engineering, Tsinghua University, Beijing, 100084, China.

Department of Biochemistry, Yanka Kupala State University of Grodno, 230030, Grodno, Belarus.

出版信息

Heliyon. 2024 Aug 15;10(17):e36265. doi: 10.1016/j.heliyon.2024.e36265. eCollection 2024 Sep 15.

DOI:10.1016/j.heliyon.2024.e36265
PMID:39263182
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11386031/
Abstract

Tunneling nanotubes (TNTs) that connect cells have been recognized as a pathway for long-range intercellular transport of diverse cargoes, including viruses, lysosomes or other organelles, Ca and electrical signals. TNTs can initially be formed from thin finger-like actin assembly-driven protrusions or cell contacts and dislodgment. However, it remains unclear whether the mechanical properties of TNTs formed by these two mechanisms are the same. Here, we developed novel microoperation methods to investigate the mechanical properties of TNTs in HEK293 cells, in which the TNTs form from thin finger-like actin assembly-driven protrusions and C2C12 cells, in which the TNTs form through contact and cell dislodgment. We found that TNTs formed by the two mechanisms represent elastic elements with similar tensile strength. In both the HEK and C2C12 cells, the tensile strength of TNTs exhibited a distinct size dependence on their lengths and diameters. Disturbing the cytoskeleton or removing extracellular Ca also changed their tensile strength. In addition, the stiffening of the extracellular matrix (ECM) enhanced the length, diameter and tensile strength of TNTs both in both HEK and C2C12 cells. Finally, a theoretical model was established to reveal the changes in the TNT's mechanical properties with its length, diameter and individual tunneling nanotubes (iTNT) number. This work not only gains insights into the properties of TNTs but also helps understand the dynamics of various cells.

摘要

连接细胞的隧道纳米管(TNTs)已被公认为是多种物质进行长距离细胞间运输的途径,这些物质包括病毒、溶酶体或其他细胞器、钙离子以及电信号。TNTs最初可由细指状肌动蛋白组装驱动的突起或细胞接触与脱离形成。然而,尚不清楚通过这两种机制形成的TNTs的力学性质是否相同。在此,我们开发了新的显微操作方法,以研究人胚肾293细胞(其中TNTs由细指状肌动蛋白组装驱动的突起形成)和C2C12细胞(其中TNTs通过接触和细胞脱离形成)中TNTs的力学性质。我们发现,由这两种机制形成的TNTs均为具有相似拉伸强度的弹性元件。在人胚肾细胞和C2C12细胞中,TNTs的拉伸强度均对其长度和直径呈现出明显的尺寸依赖性。扰乱细胞骨架或去除细胞外钙离子也会改变它们的拉伸强度。此外,细胞外基质(ECM)的硬化增强了人胚肾细胞和C2C12细胞中TNTs的长度、直径和拉伸强度。最后,建立了一个理论模型,以揭示TNTs力学性质随其长度、直径和单个隧道纳米管(iTNT)数量的变化。这项工作不仅深入了解了TNTs的性质,也有助于理解各种细胞的动态变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/9f0420fec511/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/62cfcf8ed1b7/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/88ad59dbdca5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/f30b11931488/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/868c06e7e13f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/b03fb4a60a7c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/b818bc79dae1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/f59eb36aacf0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/9f0420fec511/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/62cfcf8ed1b7/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/88ad59dbdca5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/f30b11931488/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/868c06e7e13f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/b03fb4a60a7c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/b818bc79dae1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/f59eb36aacf0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c65/11386031/9f0420fec511/gr7.jpg

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本文引用的文献

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Tunnelling nanotubes between neuronal and microglial cells allow bi-directional transfer of α-Synuclein and mitochondria.神经元和小胶质细胞之间的隧道纳米管允许α-突触核蛋白和线粒体的双向转移。
Cell Death Dis. 2023 May 18;14(5):329. doi: 10.1038/s41419-023-05835-8.
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Syncytin-mediated open-ended membrane tubular connections facilitate the intercellular transfer of cargos including Cas9 protein.合胞体连接介导的无限制膜管状连接促进包括 Cas9 蛋白在内的细胞间物质的转移。
Elife. 2023 Mar 10;12:e84391. doi: 10.7554/eLife.84391.
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Mechanical properties of tunneling nanotube and its mechanical stability in human embryonic kidney cells.
人胚肾细胞中隧道纳米管的力学性质及其力学稳定性
Front Cell Dev Biol. 2022 Sep 27;10:955676. doi: 10.3389/fcell.2022.955676. eCollection 2022.
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Formation of cellular close-ended tunneling nanotubes through mechanical deformation.通过机械变形形成细胞封闭端隧道纳米管。
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ECM stiffness-tuned exosomes drive breast cancer motility through thrombospondin-1.ECM 硬度调控的外泌体通过血栓素原-1 驱动乳腺癌的迁移能力。
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