Max Planck Institute for Medical Research, Department for Cellular Biophysics, Jahnstraße 29, 69120 Heidelberg, Germany.
Department of Neurobiology, Interdisciplinary Centre for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
Exp Cell Res. 2018 Nov 15;372(2):85-91. doi: 10.1016/j.yexcr.2018.09.012. Epub 2018 Sep 21.
Cell biology considers most animal tissues as assemblies of "individual" cells that rely on different contact-dependent communication mechanisms, including synapses, gap junctions or - a recent awareness - membrane nano- and microtubes. However, by protease-mediated singularization of dense 2D/ 3D cell cultures and tissue explants, we show here that cell collectives stay connected via a continuous meshwork of F-actin-based membrane tubes, resembling tunneling nanotube (TNT)-based networks observed between dispersed cell cultures. Fusion of respective tubes was accompanied by the ingrowth of microtubules and the invasion of mitochondria and lysosomes. Remarkably, in homology to the plasmodesmata-based plant symplast, we found evidence for expanded, membrane-based syncytia in animal tissues by observing dye transfer among the highly interlinked cells. This approach allows for the first time to visualize and quantify membrane continuity-based connections among densely packed cells and to assess their potential physiological and pathological impact closer to the in vivo situation.
细胞生物学认为，大多数动物组织都是由“个体”细胞组成的，这些细胞依赖于不同的接触依赖性通讯机制，包括突触、间隙连接或——最近才意识到——膜纳米和微管。然而，通过蛋白酶介导的密集二维/三维细胞培养物和组织外植体的单一化，我们在这里表明，细胞集体通过基于 F-肌动蛋白的膜管的连续网状结构保持连接，类似于在分散的细胞培养物之间观察到的基于隧道纳米管 (TNT) 的网络。相应的管融合伴随着微管的生长以及线粒体和溶酶体的入侵。值得注意的是，与基于胞间连丝的植物质体类似，我们通过观察高度互联细胞之间的染料转移，发现了动物组织中基于扩展的膜的合胞体的证据。这种方法首次允许可视化和量化密集包装细胞之间基于膜连续性的连接，并更接近体内情况评估它们的潜在生理和病理影响。
