Collective migration of sporozoites

Fluorescent labeled malaria plasmodium sporozoites (nucleus (blue): Hoechst; cytosol (green): GFP). Left: Plasmodium sporozoites are densely packed and propagating in a highly organized manner. Scalebar is 5 µm. Right: Collective migration of plasmodium sporozoites on a circular trajectory. Scalebar is 10 µm.

Collective migration describes the coordinated movement of larger groups of individuals and can be found in various different systems. Popular examples for collective migration can be found in schools of fish or skin cells during wound healing. In our project, we investigate the collective motion of the motile form of the malaria parasite, so-called sporozoites, which are injected into the skin of the host by a mosquito. This stage of a devastating disease killing around one million people every year is still not fully understood and thus difficult to treat. Studying the movement of sporozoites will help us to gain a fundamental understanding of their internal organization, way of propagation and dependencies on the environmental conditions. Especially the high packing density of the sporozoites within the salivary of the mosquito indicates a highly organized sorting process. Thus it is highly suggestive that interactions of sporozoites are not random but based on highly directed interactions and unique motility features.

Visualizing the trajectories is performed by applying fluorescence spinning disc microscopy and reflection interference contrast microscopy (RICM) methods. Time-resolved in vitro image sequences are quantitatively analyzed regarding parameters such as speed, characteristic trajectories, inter-active processes as well as the influence of changing environmental conditions. Moreover, the different behavior of single sporozoites compared to larger collectives is studied in detail. Mathematical modeling of the collective movement of malaria sporozoites, which is based on an agent-based approach, will reveal their way of propagation in constricted geometries as well as help to identify fundamental mechanisms of interaction and movement.

Cytosolic expressed GFP-labeled malaria plasmodium sporozoites. Time-resolved collective migration of plasmodium sporozoites on a circular trajectory. White arrows indicate the front of migration. Typically length of sporozoites is 10 µm.

Name and contact of project responsible(s):

Dr. H. Böhm (Biophysical Chemistry, Heidelberg University)
Prof. Dr. F. Frischknecht (Parasitology Unit, University Clinics Heidelberg)
Prof. Dr. U. Schwarz (Bioquant and Institute for Theoretical Physics)

Publications: n.a. for collective migration, but compare our work in single sporozoites

S. Rausch, T. Das, J. R. D. Soiné, T. W. Hofmann, C. H. J. Boehm, U. S. Schwarz, H. Boehm and J. P. Spatz. Polarizing cytoskeletal tension to induce leader cell formation during collective cell migration. Biointerphases, 8:32, 2013.

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.

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.

Anna Battista, Friedrich Frischknecht und Ulrich S. Schwarz, Geometrical model for malaria parasite migration in structured environments, to appear in Physical Review E 2014