Malaria is caused by single-celled parasites that accumulate in large groups in the salivary glands of mosquitoes before human transmission. Limited space does not allow them to actually move unless this restriction is removed through appropriate experimental training. It was in such experiments that researchers from the University of Heidelberg set in motion pathogenic microorganisms and analyzed the resulting image data using advanced image processing techniques. The data show that collectively moving pathogens form vortex systems that are largely determined by physical principles. Special computer simulations have helped identify the mechanisms underlying these rotational movements.
The collective movement of biological organisms is a common phenomenon in the natural world. Insects and fish, for example, tend to move in swarms. Often collective movement also occurs at the cellular level, for example, when cancer cells migrate from a tumor or bacteria form a biofilm. The collaboration of many people can lead to so-called emergent behavior – new characteristics that would not otherwise exist in this form. “In physics, collectivity creates important processes such as phase transitions, superconductivity, and magnetic properties,” explains Professor Dr. Ulrich Schwartz, head of the “Physics of Complex Biosystems” working group at the Institute of Theoretical Physics, University of Heidelberg. In an interdisciplinary study with Professor Dr. Friedrich Frischknecht (Malaria Research) and Professor Dr. Carl Rohr (Biomedical Image Analysis), he showed that collective movement can also occur in Plasmodium, the causative agent of malaria.
The unicellular organism is introduced into the skin through a mosquito bite, developing first in the liver and then in the blood. Because Plasmodium in most of its stages acts as a single cell, so far its collective properties have hardly been studied. In the salivary gland, the mosquito parasite has a long and curved crescent-like shape and is known as a sporozoite. “As soon as mosquitoes inject sporozoites into the skin, individual parasites begin to move rapidly to the blood vessels. This is a critical phase of infection, because it is successful only if the pathogen enters the bloodstream, “- said Prof. Frishknecht.
In their research at the Center for Infectious Diseases of Heidelberg University Hospital, Friedrich Frischnecht and his team found that parasites in infected salivary glands can be mobilized as a team. For this purpose salivary glands are cut off from a mosquito and carefully pressed between two small glass plates. The researchers were surprised to find that the crescent-shaped cells form rotating vortices in the new drug. They resemble the collective movements of bacteria or fish, although different in that they always rotate in the same direction. Thus, parasitic vortices are chiral in nature and – also unexpectedly – fluctuate in size. According to Professor Frishknecht, these fluctuations point to emerging characteristics because they are only possible in a group of motile cells and are amplified in large vortices.
To better understand these phenomena, experimental data were analyzed quantitatively. The groups of Ulrich Schwartz and Karl Rohr, head of the biomedical computer vision group at the University of Heidelberg’s BioQuant Center, used advanced imaging techniques for this purpose. They were able to track individual parasites in rotating vortices and measure their velocity and curvature. Using so-called agent-based computer simulations, it has been possible to pinpoint those laws that can explain all aspects of experimental observations. The interactions of active motion, curved cell shape, and chirality combined with mechanical flexibility are sufficient to explain the phenomena of sorting and oscillations in parasitic vortices. The fluctuations observed by scientists arise because the movement of individual pathogens is converted into elastic energy stored in the vortex. “Our new model system makes it possible to better understand the physics of teams with elastic properties and possibly make them suitable for technical applications in the future,” says physicist Ulrich Schwartz.
In the next step, researchers investigate exactly how chirality occurs. The structure of sporozoites suggests various possibilities that can be explored in experiments with genetic mutations. Initial computer simulations have already shown that parasites that rotate to the right and left quickly separate and form separate vortex systems. A better understanding of the underlying molecular mechanisms may open new avenues for sporozoite movement at the beginning of each malarial infection. “In any case, our study has shown that the mechanisms of pathogenic microorganisms play an extremely important and hitherto perceived role – a conclusion that also opens up new perspectives for medical interventions,” explains infectious disease specialist Friedrich Frishknecht.
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