Scientists unveil the complex dance of pattern-forming proteins when exposed to flow

The MinE and MinD proteins found in E. coli bacteria form the most studied pattern-forming systems in biology and this system is a serious contender to direct the cell division mechanism in synthetic cells. To uncover its secrets, German and Dutch scientists subjected the Min system to a liquid flow. They showed that the proteins form a pattern that moves, depending on the conditions, in the direction of the flow or, surprisingly, against the flow. These observations led to a new theoretical understanding of the intricate dance of these Min proteins.

Image: Min protein surface pattern, by Sabrina Meindlhumer

Patterns are omnipresent in the world, take the zebra with its black and white striped coat or the leopard with its dark spots arranged in rosettes on the body. Patterns are also observed at the cellular level. Certain proteins in cells tend to group together and localize in time and space, forming what researchers call patterns. E. coli bacteria, for example, have a system for pattern formation consisting of two proteins, called MinE and MinD.

The response of MinE and MinD proteins to flow

Sabrina Meindlhumer

But although simple, with only two proteins, the system has not revealed all its secrets. Experimentalists from Delft University of Technology in the Netherlands and theorists from LMU Munich (Ludwig-Maximilians-Universität München) in Germany combined their respective expertise to study the response of Min patterns to bulk flow. The results were published in January 2023 in Nature Communications.

“Putting cellular systems under conditions they are not usually subjected to, such as liquid flow, is a way to better understand how they work,” explained Sabrina Meindlhumer, fourth-year PhD student in Cees Dekker‘s lab at Delft University of Technology and first co-author of the paper with Fridtjof Brauns and Jernej Rudi Finžgar, from Erwin Frey’s group.

“What I observed was qualitatively in line with what Fridtjof and Jernej had predicted by simulations. Under flow, MinD and MinE proteins bind to the membrane and form protein concentration patterns in a way that depends on the ratio of MinE to MinD,” said Sabrina.

“If the MinE: MinD ratio is low, we observe patterns moving downstream. But they move upstream if the ratio is high.”

Left: Min protein surface patterns on a supported lipid bilayer (without flow). Right: Same pattern set under bulk flow, oriented from left to right. Movies acquired with a spinning disc confocal microscope. MinD is shown in magenta, MinE in green. Each movie is 5 minutes long, with one frame acquired every 15 seconds. Scale bars are 100 μm.

The Min system, a strong candidate to reproduce the mechanism of cell division

The Min system is one of the simplest model systems for pattern formation and plays an essential role in directing cell division in E. coli. MinE and MinD bind to the membrane and thus cluster in the cell in such a way that the lowest concentration of MinE and MinD is in the center of the cell. This gives other proteins involved in cell division a clue to the location of the center, which is crucial information for dividing the cell into two identical daughter cells.

In the research community, the Min system is considered a strong candidate for achieving synthetic cell division. The building of synthetic cells promises revolutionary technologies based on mimicking the natural processes of cells. But knowing how cells work is what motivates Sabrina and many researchers in this field.

“I like the fundamental aspect of research. Our goal is to have a perfect understanding of all the processes that take place in the synthetic cells we are trying to build,” she concluded.

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