Who hasn't seen it before: the view through the microscope in which a sperm penetrates an egg cell and fertilises it. This fundamental step in procreation happens dynamically and seemingly without problems. However, if you zoom in on the processes that take place during fertilisation at a molecular level, it becomes highly complex and it is thus not surprising that 15 percent of couples worldwide struggle to conceive. No microscope, however modern, can illuminate the countless interactions between the proteins involved. Therefore, the exact trigger for the fertilisation process and the molecular events that transpire just before the fusion of the sperm and egg have remained murky — until now.
With the help of simulations on "Piz Daint", the supercomputer of the Swiss National Supercomputing Centre (CSCS), a research team led by ETH Zurich Professor, Viola Vogel has now made the dynamics of these crucial processes in the fertilisation of a human egg cell visible for the first time. According to their study, which was recently published in the journal Scientific Reports, the researchers’ simulations have succeeded in revealing important secrets.
Special protein complex enables the fusion process
It was previously known that the first specific physical connection between the two germ cells is an interaction of two proteins: the JUNO, which is located on the outer membrane of the female egg cell, and the IZUMO1 on the surface of the male sperm cell. "It was assumed that the combination of the two proteins into a complex initiates the recognition and adhesion process between the germ cells, thereby enabling their fusion," says Paulina Pacak, a postdoctoral researcher in Vogel's group and first author of the study. However, based on the crystal structure scientists had not yet been able to clearly describe the mechanism.
The ETH research team finally succeeded in doing this in their latest simulations. In order to create a realistic environment in the in-silico experiment, the researchers needed to simulate JUNO and IZUMO1 in an aqueous solution. In water, however, the protein moves, and the interactions with the water molecules change both the way the proteins bind to each other and, in some cases, the function of the proteins themselves. "This makes the simulations much more complex, also because water alone already has a highly complex structure," says Vogel, "but the simulations provide a more detailed picture of the dynamic of the interactions."