Research
Biophysical determinants of malaria invasion
Our research group uses real-time live microscopy to record free Plasmodium parasites (merozoites) invading human red blood cells (figure 1), and optical tweezers to measure the detachment forces between merozoites and red blood cells during active invasion (figure 1). By combining optical tweezers with a range of inhibitors, antibodies, and genetically modified parasite strains, we can quantify the contribution of individual P. falciparum ligands to the attachment process (ref 1).
Genetic blood group resistance to severe malaria
Cell biomechanics is emerging as key determinant in Plasmodium invasion. Flickering spectroscopy combined with real-time microscopy provide a high-throughput method to correlate cell membrane biophysical properties with parasite invasion efficiency. We discovered that rigid red blood cells are less susceptible to parasite entry. (figure 2 – ref 2).
The Dantu blood group variant provides compelling evidence of how biophysical properties influence malaria resistance: its higher average membrane tension renders a larger fraction of red blood cells refractory to invasion, conferring 74% protection against severe malaria—comparable to sickle cell trait and the most effective malaria vaccines. Beyond Dantu, biophysics underlies several protective polymorphisms, including β-thalassaemia (ref 3) and Duffy-negative red blood cells (ref 4), highlighting how mechanical and molecular traits together shape host resilience to Plasmodium infection.
These insights suggest a novel therapeutic strategy of manipulating red blood cell mechanics to reduce parasite invasion.
Fever and the evolutionary balance of host–parasite survival
Fever is a universal symptom of infection and a hallmark of severe malaria, in which periodic febrile episodes coincide with the synchronous rupture of infected red blood cells and the release of parasites and toxic by-products (figure 3, left).
Our group’s research focuses on the mechanistic and evolutionary role of fever in reshaping the survival strategies of both host and parasite. To investigate this, we have developed a versatile 3D brain microvascular model embedded in a collagen hydrogel, allowing us to study how biophysical factors—particularly temperature—influence vascular obstruction, blood–brain barrier breakdown, and malaria pathogenesis. Febrile temperatures increase the binding of infected red blood cells to the vasculature. We are now exploring how heat affects ligand–receptor interactions, the extracellular matrix, and the endothelial glycocalyx (figure 3, right). These insights can guide the WHO guidelines for antipyretic administration and vessel-protective therapies.
Left: fever cycles during malaria infection are synchronised with parasite development.
Right: a brief exposure of endothelial microvessels to febrile temperatures enhances infected red blood cell adhesion in a 3D engineered model with controlled geometry and flow dynamics.
Contact
Research Group Viola Introini
Max-Planck-Zentrum für Physik und Medizin
Kussmaulallee 2
Room 01.220
91054 Erlangen, Germany
+49 9131 8284 153
