Ruprecht Karls Universität Heidelberg


Biophysics of malaria parasite migration

Running in circles. Sporozoites are the form of the malaria parasite which is injected by the mosquito into the skin of the host. On flat substrates, they usually run in circles (here with colour-coded time). In three-dimensional tissue, they move in spirals. These peculiar movement patterns are believed to result from their internal organization, although these observations demonstrate that the environment also plays an important role. Traction patterns of sporozoites. Using soft elastic substrates, we have shown that sporozoite movement proceeds in cycles of attachement, elongation and rupture, which mainly result from large adhesions at the front and back of the banana-shaped parasite. The left image shows a GFP-marked parasite on an elastic substrate with two differently coloured types of fluorescent beads. The middle and right images show the force vectors and magnitudes, respectively, of the traction patterns reconstructed from the displacement data.

In close collaboration with the groups of Friedrich Frischknecht and Joachim Spatz, we have analyzed how malaria parasites migrate as they enter the skin of their host. At this stage, they exist as worm-like and banana-shape sporozoites (in later stages of the lifecycle, they completely change their phenotype). Using reflection interference contrast microscopy and traction force microscopy on soft elastic substrates, we have shown that sporozoites move in cycles of attachement, elongation and rupture mediated by variable regions of close approach between parasite and substrate. These regions typically move with the parasite and are thought to correspond to adhesion through TRAP-receptors (Cell Host Microbe 2009). Investigating sporozoite movement in pillar assays, we also demonstrated that the typical motion patterns of sporozoites in tissue can be caused by external obstacles, suggesting that chemotaxis plays at most a minor role in the way sporozoites navigate from the site of injection to the blood vessels, from where they proceed to the liver (PLoS Pathogens 2011).

Publications:

  • S. Münter, B. Sabass, C. Selhuber-Unkel, M. Kudryashev, S. Hegge, U. Engel, J. P. Spatz, K. Matuschewski, U. S. Schwarz, and F. Frischknecht. Plasmodium sporozoite motility is modulated by the turnover of discrete adhesion sites. Cell Host Microbe, 6:551-562, 2009. (abstract, doi:10.1016/j.chom.2009.11.007, PDF)
  • J.K. Hellmann, S. Münter, M. Kudryashev, S. Schulz, K. Heiss, A.-K. Müller, K. Matuschewski, J.P. Spatz, U.S. Schwarz, and F. Frischknecht. Environmental constraints guide migration of malaria parasites during transmission. PLoS Pathogens, 7:e1002080, 2011. (abstract, doi:10.1371/journal.ppat.1002080, PDF)


Last modified Di 4. Okt 17:45:17 CEST 2011 by USS.
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