Malaria parasites form vortices | EurekAlert!


Image: The figure combines the confocal microscope image of sporozoite vertebrae with the snapshot of an agent-based computer simulation of these vertebrae.
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Source: Group Frischknecht and Group Schwarz (Paper in Nature Physics)

The disease malaria is caused by unicellular parasites that accumulate in large groups in the salivary glands of mosquitoes before being transmitted to humans. The limited space there prevents them from actually moving unless this restriction is removed by appropriate experiment preparation. In such experiments, researchers at Heidelberg University set the pathogens in motion and analyzed the image data obtained using the latest image processing methods. The data show that the pathogens moving together form vortex systems that are largely determined by physical principles. Special computer simulations helped to identify the mechanisms underlying these rotary movements.

The collective movement of biological organisms is a widespread phenomenon in nature. Insects and fish, for example, tend to move in schools. Collective movement often also takes place at the cellular level, for example when cancer cells migrate from a tumor or bacteria form a biofilm. Through the cooperation of many individuals, so-called emergent behavior can arise – new properties that would not otherwise exist in this form. “In physics, important processes such as phase transitions, superconductivity and 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 together with Prof. Dr. Friedrich Frischknecht (malaria research) and Prof. Dr. Karl Rohr (biomedical image analysis) he showed that collective movement can also occur in Plasmodium, the causative agent of malaria.

The protozoa is injected into the skin through a mosquito bite and develops first in the liver and later in the blood. Since Plasmodium functions as a single cell in most of its stages, its collective properties have been little studied. In the mosquito’s salivary gland, the parasite has a long and curved shape, resembling a crescent moon, and is known as a sporozoite. “Once sporozoites are injected into the skin by the mosquito, individual parasites begin to move rapidly towards the blood vessels. This is the critical phase of the infection, because it only succeeds if a pathogen gets into the bloodstream,” emphasizes Prof. Frischknecht.

In their studies at the Center for Infectious Diseases at Heidelberg University Hospital, Friedrich Frischknecht and his team discovered that the parasites in infected salivary glands can be mobilized collectively. To do this, the mosquito’s salivary glands are cut off and carefully pressed between two small glass plates. The researchers were surprised to find that the crescent-shaped cells in the new preparation form rotating whorls. They are reminiscent of the collective movements of bacteria or fish, but differ in that they always rotate in the same direction. The parasite whorls therefore have a chiral character and – also unexpectedly – ​​fluctuate in size. According to Prof. Frischknecht, these oscillations indicate emergent properties, since they are only possible in the collective of moving cells and become stronger in larger vortices.

In order to understand these phenomena in more detail, the experimental data were analyzed quantitatively. The groups led by Ulrich Schwarz and Karl Rohr, heads of the Biomedical Computer Vision Group at the BioQuant Center of the University of Heidelberg, used the latest image processing methods. They were able to track individual parasites in the rotating vortices and measure both their speed and curvature. Using 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 cell shape and chirality in conjunction with mechanical flexibility is sufficient to explain the sorting and vibrational phenomena in the parasite whorls. The vibrations observed by the scientists arise because the movement of the individual pathogens is converted into elastic energy, which is stored in the vortex. “Our new model system offers the opportunity to better understand the physics of collectives with elastic properties and perhaps make it usable for technical applications in the future,” says physicist Ulrich Schwarz.

In the next step, the researchers will investigate how exactly the chirality of the movement comes about. The structure of sporozoites suggests several possibilities that can be explored in genetic mutation experiments. First computer simulations have already shown that the right-hand and left-hand rotating parasites quickly separate and create separate vortex systems. A better understanding of the underlying molecular mechanisms could open up new ways to disrupt sporozoite movement at the onset of each malaria infection. “In any case, our study has shown that the mechanics of the pathogens play an extremely important and previously overlooked role – a finding that also opens up new perspectives for medical interventions,” explains the infectiologist Friedrich Frischknecht.

The research work was carried out as part of the Collaborative Research Center 1129 “Integrative Analysis of Pathogen Replication and Spread” at the Heidelberg Medical Faculty of the University of Heidelberg. The results of the interdisciplinary study were published in the journal natural physics.

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