[Professors Jong-Bong Lee and Jae-Hyung Jeon’s research team at POSTECH identifies the formation mechanism of close-ended tunneling nanotubes.]

A sky bridge connecting two mountain peaks may look dangerous but it safely lets hikers walk across. There are also tiny passageways that connect distant cells called tunneling nanotubes (TNT) in our body. How are these intercellular nanotubes made, which are known to transport a variety of substances from calcium – that is essential to life – to harmful viruses?

Professor Jong-Bong Lee (Department of Physics & School of Interdisciplinary Bioscience and Bioengineering), Professor Minhyeok Chang and Ph.D candidate Gayun Bu (Department of Physics), Professor Jae-Hyung Jeon and Assistant Professor O-Chul Lee (Department of Physics), and Professor Sung Ho Ryu (Department of Life Sciences) at POSTECH, in collaboration with Professor Junsang Doh (Seoul National University), Professor Sang-Hee Shim (Korea University), Professor Hyung-Bae Kwon (Johns Hopkins University), and Professor Kolomeisky (Rice University) have identified the principle behind the formation of close-ended tunneling nanotubes.

The findings from this study were recently published in the international academic journal Science Advances (DOI: 10.1126/sciadv.abj3995).

Tunneling nanotubes connect cells and have a delicate and long structure, which is hundreds of nanometers (nm, 1 nm = 1 billionth of a meter) thick and extends over several tens of micrometers (μm, 1 μm = 1 millionth of a meter), which is 100 times its thickness. But how these seemingly fragile tubes form between distant cells and remain robust for hours have remained under wraps.

The POSTECH research team used super-resolution microscopy and optical tweezers to successfully capture the formation process of tunneling nanotubes in this study.

Many cells have tentacles called filopodia, and when the filopodia of adjacent cells come into contact with each other, they bind through cell adhesion molecules called cadherin. At this time, the filopodia grow in length through helical deformation.

Due to this helical deformation, two filopodia become twisted with each other and when one of the two filopodia is connected to the other cell first, the remaining unconnected one comes off and retracts. The researchers have confirmed that the one filopodium left in this manner becomes a close-ended tunneling nanotube. Based on the experimental results, the research team demonstrated that such a model is physically feasible through biophysical theories and computer-assisted simulations.

The research team also confirmed that calcium ions are transported between cells through these close-ended TNT. Despite their closed structure, a channel is formed between the tip of the nanotube and the cell, allowing materials to enter and exit.

The findings from this study are anticipated to be applicable in cancer research in the future because tunneling nanotubes, often formed in cancer cells, have shown pathological importance in tumor metastasis.

This study was conducted with the support from the overseas faculty training program of the LG Yonam Foundation and from the Global Research Lab Program, the Mid-career Researcher Program, and the Creative and Transformative Research Program of the National Research Foundation of Korea.