How do the cells in our body sense their surroundings?

Cells have a reliable sense of smell that allows them to grow in the right direction, depending on the source of the smell. Researchers have now been able to understand how the sense of smell works in cells.

A common problem facing cells is that they are surrounded by a cloud of odors and need to determine the direction of their source. Nerve cells, for example, create long extensions that extend in the direction of the signals arriving from other cells, this in order to create the network that constitutes the nervous system; Similarly, scavenger cells detect the odor of harmful bacteria in order to chase them down and destroy them. But how do the cells manage to smell these signals, which become weaker and weaker with distance from the source? How do cells "read" this waning signal - known as a signal cascade - in order to direct the direction of their growth or their movement towards the source of the signal? The way in which cells locate signals in space is an important question in the field of biology - to this day this puzzle remains without a proper answer.

Now, the solution may have been found by a team of researchers led by Professor Matthias Peter, from the Zurich Institute of Technology (ETH). Yeast cells have a highly sensitive multifunctional device that detects chemical signals, processes them accordingly, and initiates the appropriate response - growth towards the source of the signal. Thus, yeast cells are able to "smell" the location of possible partners for reproduction in their environment, and thus they can move towards them. The biologists conducted their research using a combination of microscope observations and a computer model they developed in interdisciplinary collaboration with other researchers. If the cell suspects that a signal cascade is found in its vicinity, it places its detection means in a random position on the membrane. This medium is a large protein consisting of more than a hundred different components; The protein is so large that it can be detected under a fluorescence microscope. The researchers call this situation the 'site of polarity' because polar growth occurs at that location.

Using a fluorescence microscope, the researchers were able to observe how the site of polarity locates the source of the signal cascade. In the first step, the site moves along the membrane to the point where the signal is strongest. As soon as it detects the strongest signal, that is - the concentration of the signal in the cascade is the highest - it stops moving. In the next step, the site creates a bulge in the cell at this point, a bulge that continues to expand towards the signal source. Naturally, the signal is generated by the reproductive partner and the two cells fuse as soon as they meet each other.

In order to understand the molecular mechanisms of this process, the researchers used a computer model. "This model helped us reduce the complexity of the polarity site and the process to only a small number of essential components," says one of the researchers, who was also involved in the article published in the scientific journal Developmental Cell. These essential components include the receptor that receives the signal and passes it on; Other components include the protein Cdc42, which transports the receptor through the cell membrane, and the protein Cdc24, which regulates the activity of the protein Cdc42. "You can imagine the receptor as the nose, the Cdc42 protein as the steering wheel of the machine and the Cdc24 protein as its brakes," explains the lead researcher. While the polar site moves along the cell membrane looking for the strongest chemical signal, only a few molecules of the Cdc24 protein are inside the machine itself. As soon as it locates the point where the signal concentration is the highest, the polar site, the so-called nose, requests and receives additional Cdc24 molecules, which are normally stored in the cell nucleus. The more Cdc24 molecules arrive, the slower the machine runs. At the same time, only when their number reaches a certain threshold, the polar site stops its activity and starts creating the protrusion in the cell.

"Initially, we were able to detect the movement of the polar site with the help of a fluorescence microscope. In the next step we simulated this movement in a computer model, which allowed us to formulate the hypothesis regarding how this movement could be controlled. In the next step, we were able to experimentally verify our hypothesis by introducing mutations into the cells and using a fluorescence microscope," explains the researcher. He adds and points out that the simple computer model they formulated allowed them to have an excellent basis for designing experiments in which they could change the components quickly and identify the important elements. The model made the research simpler, since it made unnecessary the need to perform many experiments.

The researchers estimate that not only the yeast cells use this means of detection - a similar behavior has also been observed in roundworms, without a molecular explanation so far. Researchers at the Zurich Institute of Technology have now provided the logical explanation and described in great detail, for the first time ever, how cells manage to detect and sense the signal cascade. This study paves the way for further studies in the field of sensing spatial signals by cells - both in yeast cells and in human cells. One of the researchers points out: "Despite the fact that we currently do not see direct medical applications growing from this research, in the distant future the findings could bring great benefit to the well-being of humanity. At the moment, the findings mainly constitute an important advance in the basic research of cell behavior".

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