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Malaria parasites are making a fuss

The disease malaria is caused by unicellular parasites that accumulate in large groups in the salivary gland of the mosquito before being transmitted to humans. Due to the spatial confinement, they cannot actually move there, unless this restriction is lifted by a suitable experimental preparation. In such experiments, scientists from the University of Heidelberg set the pathogens in motion and evaluated the recorded image data using modern image processing methods. The data show that the collectively moving pathogens form vortex systems that are strongly governed by physical principles. With the help of special computer simulations, the mechanisms underlying these rotating movements could be determined.

The collective movement of biological organisms is a widespread phenomenon of the natural world. Insects and fish like to move in swarms. A movement in the collective also often takes place on the cellular level, for example when cancer cells migrate from a tumor or bacteria form a biofilm. The interaction of many individuals can lead to so-called emergent behavior – new properties that would not otherwise exist in this form. “In physics, important processes such as phase transitions, superconductivity or magnetic properties arise as a result of collectivity,” explains Prof. Dr. Ulrich Schwarz, head of the “Physics of Complex Biosystems” working group at the Institute for Theoretical Physics at Heidelberg University. In an interdisciplinary study he has now with Prof. Dr. Friedrich Frischknecht (malaria research) and Prof. Dr. Karl Rohr (biomedical image analysis) showed that collective movement can also occur in the malaria pathogen Plasmodium.

The protozoa is transmitted to the skin by a mosquito bite and then continues to develop first in the liver and then in the blood. Since Plasmodium acts as a single cell in most stages, its collective properties have rarely been studied. In the mosquito’s salivary gland, the parasite has a long and curved shape resembling a crescent moon called a sporozoite. “Once sporozoites are injected into the skin by the mosquito, rapid movement of individual parasites towards the blood vessels begins. This is the critical phase of the infection, as it is only successful if a pathogen reaches the bloodstream,” emphasizes Prof. Frischknecht.

In their investigations at the Center for Infectious Diseases at Heidelberg University Hospital, Friedrich Frischknecht and his team discovered that the parasites contained in the infected salivary glands can be mobilized collectively. To do this, the salivary gland is removed from the mosquito and gently pressed between two small glass plates. It is an unexpected discovery for the scientists that the crescent-shaped cells form rotating whorls in the new preparation. They are reminiscent of the collective movements of bacteria or fish, but differ from them in that they always turn in the same direction. The parasite vortices therefore have a chiral character and – also unexpected – show fluctuations in their size. According to Prof. Frischknecht, these oscillations indicate emergent properties, since they are only possible in the collective of moving cells and become stronger with larger vortices.

In order to better understand these phenomena, the experimental data were evaluated quantitatively. The groups led by Ulrich Schwarz and Karl Rohr, heads of the Biomedical Computer Vision Group at the BioQuant Center at Heidelberg University, used modern image processing methods. They were able to track individual parasites in the rotating vortices and measure their speeds and curvatures. With the help of so-called agent-based computer simulations, it was possible to identify exactly those laws that can explain all aspects of the experimental observations. The interplay of active movement, curved shape of the cell and chirality in connection with mechanical flexibility is sufficient to justify the sorting and oscillation phenomena in the parasite whorls. The oscillations observed by the scientists arise from the fact that the movement of the individual pathogens is converted into elastic energy, which is stored in the vortices. “Our new model system offers the opportunity to better understand the physics of collectives with elastic properties and to make them usable for technical applications in the future,” emphasizes physicist Ulrich Schwarz.

In a next step, the researchers will investigate how exactly the chirality of the movement arises. The structure of sporozoites suggests several possibilities that can be explored in genetic mutation experiments. The first computer simulations have already shown that right- and left-handed parasites quickly “unmix” and create separate vortex systems. A better understanding of the underlying molecular mechanisms could open up new ways to disrupt the movement of sporozoites that are at the origin of every malaria infection. “Our study has definitely shown that the mechanics of the pathogens play a very important, previously overlooked role – a finding that also opens up new perspectives for medical interventions,” says infectiologist Friedrich Frischknecht.

The work was carried out in the Collaborative Research Center 1129 “Integrative Analysis of the Replication and Spread of Pathogenic Pathogens”, which is funded by the German Research Foundation and is located at the Heidelberg Medical Faculty of the University of Heidelberg. The scientists have published the results of their interdisciplinary study in “Nature Physics”.

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