It is a rather trivial statement: if you want to enter the house through a door, it is best to take a key in your hand, open and go inside. But if you have no idea what the key looks like or where it is hidden – under the doormat, on the basement stairs? – it becomes much more difficult.
It is similar in biology. It goes without saying that there are doors that connect the interior of cells to the exterior. One of these doors, however, still puzzles scientists: so-called “lipid rafts”. These are certain areas in the cell membrane in which lipids, which are important for the signal transmission of cells, accumulate. These are platform enriched with cholesterol that looks like rafts, these areas “float” through the cell membrane. Across lipid rafts, molecules can also enter and get out of the cell.
In particular, scientists suspect that these “lipid rafts” are also contributing to diseases such as Parkinson, Alzheimer or HiV infection, whose pathogens enter the cells via these lipid raft. An understanding of this mechanism is therefore fundamental to the emergence of such diseases.
However, no one has been able to fully characterize “lipid rafts” in living cells, so far their size and lifetime are still subject to vigorous debates. Only in model membranes have the “rafts” been observed and fully characterize but “these models were not very well transmissible to real cells”, explains Dr. Jean-Baptiste Fleury (Saarland University).
The expert in microfluidics explains why this is the reason: “On the one hand, previous experiments were very large, namely in the micrometer range. At the cell level, however, the processes take place at the nanometer level, i.e. again by a factor of 1000 below. In addition, the lipid rafts in the experiment have been much more short-lived than in real cells”, Fleury explains. Instead of between one and 15 milliseconds, the previous experimental lipid rafts existed only for about 10 nanoseconds, i.e. about one millionth of the natural lipid rafts.
Jean-Baptiste Fleury has now developed an experiment system that brings both the size scale, the temporal dimension of these lipid rafts much closer to the natural conditions than has been the case up to now. To do this, he placed around 10 nanometer long carbon nanotubes, as a replacement of an artificial transmembranar protein, inside the model membrane to trigger the formation of ultra-small cholesterol region around this carbon nanotube. He was able to observe that the cholesterol concentration plays a decisive role in whether the nanotubes got through the cell or whether they remained trapped in the cell membrane. “We found that nanotubes in presence of high cholesterol concentrations can spontaneously emerge from the bilayer within a few milliseconds while remaining trapped in the membrane if the bilayer does not contain cholesterol.”
Theoretical physicists from the University of Rovira i Virgili in Tarragona (Spain) and the Nanjing University in China developed the basis for this. In months of computer simulations, they calculated the behavior of the nanotubes and cholesterol and then used the Saarland expertise of Jean-Baptiste Fleury as an experimental physicist to check the theoretical knowledge in the experiment. In this way, the international research team has developed fundamental new approaches to researching lipid raft, so that the development of diseases and the cellular processes may also be better understood. They published their findings in the renowned journal “Physical Review Letters“.
Guo, Y., et al. (2020) Unexpected Cholesterol-Induced Destabilization of Lipid Membranes near Transmembrane Carbon Nanotubes. Physical Review Letters. doi.org/10.1103/PhysRevLett.124.038001.