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Cells coupling together through a nanotube (arrow)  (Source: University of Bergen)
Cells use nano-thin membrane tubes and gap junctions to send electrical signals to one another

Researchers from the University of Bergen's Department of Biomedicine have discovered new details associated with how cells communicate, which could eventually contribute to our knowledge of cell activity during processes like the healing of wounds.  

Dr. Xiang Wang and Professor Hans-Hermann Gerdes, who are researchers from the University of Bergen's Department of Biomedicine, have studied how electrical signals are passed from cell to cell, and found that nano-thin membrane tubes and gap junctions together made it possible for cells to transmit these signals. By learning how tunneling nanotubes (TNTs) allow cells to couple and communicate, scientists hope to learn how cells perform certain tasks like developing tissue in the embryo.

Wang and Gerdes made the discovery when applying a fluorescent dye to cells that were connecting through the formation of a nanotube. As the electric potential of the cell membrane changes, the dye changes in intensity. As two cells formed a connection through a nanotube, a microinjection needle was used to depolarize the cell's membrane potential, which made the dye on the cell membrane light up. On the other end of the nanotube, the fluorescent indicator lit up as well. Wang noted that this is a characteristic most cells possess, but not all.  

The nanotubes only last a few minutes, which makes it difficult for scientists to figure out when and where the cells will form the nanotubes. To better track these formations, Wang and Gerdes created a micro-matrix that consists of "thousands of points and bridges on a plate surface." Nano-structured material is then placed on the plate to allow cells to stick. At each point, a cell is placed in hopes of nanotubes being formed along the bridges, and a camera is used to catch the creation of nanotubes. The microscope takes 50 preselected pictures every five minutes.  

While it is important to further understand the formation of the nanotubes, the nanotubes alone do not allow cells to transmit electrical signals. According to Wang, gap junctions, which consist of a ring-shaped proteins, always connect one end of the nanotube to cells before the cell transmits electrical signals. In some other cases, electrical signals sent to the membrane of the receiving cell via nanotube enter after the membrane is depolarized and a calcium channel opens. This helped push the signals along. 

"In other words, there are two components: a nanotube and a gap junction," said Gerdes. "The nanotube grows out from one cell and connects to the other cell through a gap junction. Only then can the two cells be coupled electrically." 

Wang and Gerdes hope that this sort of research can lead to the understanding of how cells group together to heal wounds, and how cells create tissue in the embryo.  

"It's quite possible that the discovery of nanotubes will give us new insight into intercellular communication," said Gerdes. "The process could explain how cells are coordinated during embryo growth. In that phase, cells travel long distances -- yet they demonstrate a kind of collective behavior, and move together like a flock of birds can."

The researchers also hope that to find that this method of electrical impulse transfer is present in human brain cells. This could lead to a better understanding of brain function overall. 

This study was published in Proceedings of the National Academy of Sciences.





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