Amoebae: Master Tunnel Builders

How do single-celled organisms communicate with one another? Which channels do they use when danger threatens? An international research team from the Leibniz-HKI and the Cluster of Excellence »Balance of the Microverse« has now shown that social amoebae, in addition to known communication pathways, also make use of a particularly direct route: tiny membrane tunnels that connect neighbouring cells. These »nano-pipelines« serve the microbes as both a communication and transport system for important cellular components—a potential »first-aid network«. The study, recently published in the journal PNAS Nexus, provides new insights into how single cells may have evolved into complex multicellular organisms such as plants, animals and humans.

Social amoebae are remarkable organisms: They usually live as independent single cells in the soil. When food becomes scarce, however, they come together to form multicellular fruiting bodies. Their spores can reach new locations with more abundant food, much like dandelion seeds. Until now, experts had assumed that microorganisms communicate primarily via chemical signalling molecules that they release into their environment—much like a message in a bottle in the ocean.

A dynamic communication system of nanotubes

A team from the Leibniz Institute for Natural Product Research and Infection Biology—Hans Knöll Institute (Leibniz-HKI) and the Cluster of Excellence »Balance of the Microverse« at Friedrich Schiller University Jena, working with research teams in Cambridge, UK, and Bengaluru, India, has now discovered that amoebae also use a kind of direct tunnel connection. Using high-resolution live-cell microscopy, the researchers detected structures known as tunneling nanotubes (TNTs) in amoebae. These tiny membrane tubes can reach lengths of more than 200 micrometres – for an amoeba, that’s the equivalent of a massive bridge connection.

»Capturing images of these microscopic tunnel connections was a real technical challenge for us,« says the study’s first author, Dr Harikumar R. Suma. »Amoebae are definitely not fans of bright light sources and quickly move away when illuminated. This causes the tunnel connections to snap rapidly, making these cellular bridges visible for only a few fleeting moments. We therefore had to keep pace with these fast-moving cells.«

Expanding the tunnel network under stress

Particularly surprising was how the amoebae reacted under stress. To induce this stress, the researchers experimentally disrupted actin, a protein that forms a crucial part of the cells’ internal scaffolding, helps them maintain their shape and move, and also supports the nanotubes themselves. Yet the amoebae did not stop building tunnels during the stress test. Instead, they formed around 25 times as many tunnels as under normal conditions.

Inside the tunnel system, the researchers observed special cargo moving between neighbouring cells, including cellular components such as mitochondria—the »powerhouses of the cell«. The same transport was also observed in the weakened cells subjected to the stress test. »This behaviour resembles a cellular first-aid network. The amoebae appear to use the tunnel connections to pass on important cellular components. Further studies are needed to determine exactly what role this transport mechanism plays under stress,« Suma explains.

Tracing the evolution of cell communication

The findings, published in the journal PNAS Nexus, extend far beyond microbiology. Until now, such or similar tunnel connections had mainly been known from mammalian cells and bacteria. The discovery that comparatively early-branching single-celled organisms such as amoebae also possess this ability provides new clues about early forms of cell communication.

»For multicellular life to evolve, individual cells had to learn to cooperate closely,« explains Prof. Pierre Stallforth, professor at Friedrich Schiller University Jena and head of Palaeobiotechnology at the Leibniz-HKI. »The nanotubes of amoebae reveal a direct mechanism that may have enabled this kind of cooperation on the path towards multicellularity.«

International expertise

For the study, the team brought together complementary expertise. Robert R. Kay from the MRC Laboratory of Molecular Biology in Cambridge brought his long-standing experience with the social amoeba, Dictyostelium to the collaboration. Sandeep M. Eswarappa from the Indian Institute of Science in Bengaluru contributed his expertise on tunneling nanotubes in mammalian cells, strengthening the study’s cell-biology perspective in particular. Together with Harikumar R. Suma and Pierre Stallforth from the Leibniz-HKI, the team gained new insights into a field of research that exemplifies the goal of the Cluster of Excellence »Balance of the Microverse«: to improve our understanding of interactions between microorganisms and their importance for the balance of microbial communities.

The research project was funded by the German Research Foundation (DFG) under Germany’s Excellence Strategy—Cluster of Excellence »Balance of the Microverse« at Friedrich Schiller University Jena.