Why are cell membranes asymmetrical

Asymmetry thanks to perfect balance - Max Planck scientists work with US researchers to develop a mathematical model for polarity in cell membranes

Cell polarity is the prerequisite for many of the most important cellular processes, such as the secretion of substances, the transmission of signals, local growth and also the division of cells. To do this, however, specific molecules have to accumulate in certain areas of the cell membrane. Dr. Roland Wedlich-Söldner from the Max Planck Institute for Biochemistry in Martinsried has now been able to show, in collaboration with US scientists, how this so-called cortical polarity is created. The researchers combined measurements on living cells with a mathematical model they had developed in order to analyze the influence of the decisive mechanisms in the asymmetric distribution of membrane proteins. The data show, among other things, that the cells can set up polarized membrane regions with almost perfect precision. This novel approach is an important step on the way to a spatially and temporally quantifiable model of the cell. (Cell, April 20, 2007)

In a sense, the components of a cell membrane can be compared to balls on the surface of water. In both cases it is difficult to keep the particles in a certain order. Rather, they strive for a uniform distribution through to complete mixing - they diffuse. This can also be observed in cell membranes because they resemble a liquid film that allows its components to move sideways. However, for the normal function of the cell, an asymmetrical distribution of the membrane proteins is often necessary, which must be present in locally increased concentrations. This so-called cortical polarity is, among other things, a prerequisite for local cell growth, cell division and other essential processes, especially in the embryonic development of organisms. For this, however, the molecules that are important for the respective process must accumulate in specific areas of the cell membrane despite their attempt to diffuse - and remain there long enough to fulfill their function. This is possible when active transport processes superimpose the diffusion effect to such an extent that the necessary particle density is achieved.

“We wanted to know which principles are based on the formation and maintenance of an asymmetrical distribution of molecules in the cell membrane and also quantify their influence,” says Wedlich-Söldner. In addition to diffusion, which counteracts a locally increased molecular density, two cellular mechanisms in particular influence the concentration of membrane proteins in most model organisms and systems. On the one hand, this is the active transport of particles along cellular support structures, and on the other hand, endocytosis, i.e. the uptake of membrane molecules into the cell with the help of small membrane vesicles, the vesicles. For their investigation, the scientists chose a model system that has already been well characterized: cells from baker's yeast Saccharomyces cerevisiaethat produce the active form of Cdc42, the key protein in cell polarity. Mutations in Cdc42 can - if the polarity is disturbed as a result - promote the development of cancer. Some activators of the protein can also trigger tumor growth as so-called oncogenes in a defective state.

If the concentration of Cdc42 or another molecule is increased locally in the cell membrane, this is a prerequisite for the formation of a so-called “cap” at this point, which in turn is the starting point for the formation of a daughter cell during cell division. "One of the decisive factors in cap formation is of course that enough Cdc42 accumulates at the relevant point on the cell membrane," reports Wedlich-Söldner. “But it is just as important that the cap region runs with the sharpest possible border. We were able to show for the first time that endocytosis is primarily responsible for this. During this process, vesicles are pinched off from the entire cell membrane, and thus also from the cap region, which, among other things, remove Cdc42. In contrast to the border region, however, the molecule continues to be supplied in the center of the cap by active transport, and the loss of Cdc42 is compensated for. We don't yet know the exact mechanism, but with the help of our model we were able to prove that the cells can delimit their caps in this way with almost maximum spatial precision. "

Overall, the scientists were able to show that a balance of diffusion, active transport and endocytosis is sufficient to describe the process of polarization on the cell membrane with high accuracy. "The biological model system we have chosen is relatively simple and therefore particularly well suited for analysis," says Wedlich-Söldner. “In this way, we have also succeeded in examining and quantifying the interaction of these three important mechanisms for the first time at the system level and with the help of a single mathematical model. Our data are an important step on the way to a better understanding of how biological systems dynamically and very precisely generate an asymmetric distribution of molecules in the cell membrane. We assume that our results are almost universally valid: In this case, the yeast cells were only a model for the abstract mathematical approach, and the mechanisms of cortical polarity that we analyzed are also from a large number of organisms, from unicellular organisms to higher animals , known. "(SW)

Original publication:

Eugenio Marco, Roland Wedlich-Söldner, Rong Li, Steven J. Altschuler, and Lani F. Wu: Endocytosis Optimizes the Dynamic Localization of Membrane Proteins that Regulate Cortical Polarity. Cell 129, 411-422, April 20, 2007.

Contact:

Dr. Roland Wedlich mercenaries

Max Planck Institute for Biochemistry, Martinsried

Tel .: +49 89 8578-3410

Email: [email protected]