&Bullet; physics 14, 40
Unexpected behavior of a protein involved in cell division could indicate the possible function of this molecule in earlier life forms.
Petra Schwille is looking for the “hydrogen atom” in biology, the simplest element of life, the behavior and properties of which scientists can fully calculate. The search led Schwille to delve into the mysterious world of proteins, where she and her group at the Max Planck Institute for Biochemistry in Germany discovered some unprecedented protein behaviors. There is no evidence that these behaviors have any function in cells today, but they could reveal the role of protein in earlier life forms and thus potentially enable scientists to solve the mystery of the beginning of life. Schwille discussed the work of her group at the recent annual meeting of the Biophysical Society.
Proteins are the functional elements of life that control everything from DNA replication to metabolic reactions to the transport of molecules from one part of a cell to another. Without these functions, life as we know it would not exist, which is why, says Schwille, over the past ten years she has tried to decipher the hidden behavior of these molecules. “I’m really very fascinated by what proteins can do. I think if we understand their functions and how these functions come about, there is a very real possibility of understanding the secrets of life. “
The proteins that are currently the focus of Schwille’s attention have the catchy names “MinD” and “MinE”, pronounced as “mindy” and “minny”. Found in E. coli Bacteria, Min proteins drive cell division by creating patterns on the cell membrane that tell the bacteria where to split. “Basically, the Min proteins ensure that the center of the cell is found so that two daughter cells of the same size are obtained after division,” says Schwille. Biologists also believe that the proteins are involved in ensuring that each daughter cell inherits the same amount of chromosomes, but that has yet to be confirmed.
The ability of cells to divide – or reproduce – is one of three essential properties that make them come alive. (The other two are the ability to metabolize and the ability to process information.) If one is to build the hydrogen atom of biology, then “it is crucial to understand and replicate the process of cell division,” says Schwille, and that is exactly it what she and her team were trying to do with MinD and MinE.
In their experiments, the group begins with an idealized cell membrane, which they assemble on a glass slide immersed in a solution. Then they add purified Min proteins, which they have doped with a fluorescent molecule, and adenosine triphosphate (ATP) molecules – the energy source for most cell processes – to the system and observe what happens with a microscope.
Their first experiments, which they completed more than a decade ago, showed that MinD and MinE self-organize on the membrane, creating undulating patterns in the concentrations of the two proteins. These patterns extend over many hundreds of micrometers and persist for many hours. Later experiments confirmed that the patterning process sets the stage for cell division, with a drop in Min protein concentrations in the center of the membrane. “The proteins have this nice self-organizing ability that requires very little complexity – you need the proteins, ATP and a membrane, and that’s it,” says Schwille.
While much of the team has focused on understanding the known roles of proteins in real cells, their exploration has revealed some unexpected functions. In a series of experiments with a spherical membrane structure (known as a vesicle), Schwille and her group found that the self-organization of the Min proteins induced local concentration peaks that changed the surface tension of the vesicle and the curvature of its membrane. Depending on the size of the peaks, the vesicles either bounced up and down or opened and closed like a fish’s mouth. In another group of experiments, this time again on flat membranes, they found out that MinD and MinE concentration waves can exert a rousing force on other proteins sitting on the membrane.
But these behaviors only occur in their idealized systems – they have never been seen in real cells. This environmental sensitivity could shake a basic belief in biology that every protein plays a very clear role and will behave in the same way in every organism, says Schwille. “That is clearly not the case.” Rather, the experiments of her group show that a protein can have one function in one organism and a completely different function in another.
“I really like the idea of ’moonlighting’ proteins, where a protein has more than one physiologically relevant biochemical or biophysical function,” says Allen Liu, a biophysicist at the University of Michigan. Liu was not involved in this project, but is familiar with Schwille’s work as he visited her laboratory during his sabbatical year. He finds it particularly interesting that the black light proteins in this case involve cell division, “since changes in the shape of the cells underlie many essential cellular processes”.
Observing these hidden behaviors could help in the search for the origin of life, says Schwille. The Min proteins, for example, may not have their crucial role in organisms today, but that doesn’t mean they didn’t fulfill that role in earlier organisms, she says. “It is very unlikely that these functions, these very obvious functions, have never been used by a cell.”
Ricard Solé, biophysicist at the University of Pompeu Fabra, Spain, finds this evolutionary aspect of the work interesting. Inducing curvature changes in the cell membrane is key to cell division, but it remains unknown how early cells developed the mechanisms for reliable self-replication, he says. These results could help “untangle” this problem.
Katherine Wright is assistant editor of physics.