Dr. Anil Kumar Dasanna (Saarbrücken / DE; Juelich / DE), Dr Sebastian Hillringhaus (Juelich / DE), Prof. Gerhard Gompper (Juelich / DE), Dr Dmitry Fedosov (Juelich / DE)
Abstract text
Invasion of plasmodium merozoites into erythrocytes is an essential step for their survival and multiplication. The parasites align their apex with the membrane surface for successful invasion. It has been hypothesized that they use erythrocyte membrane deformability to efficiently align themselves. We use computer simulations to test the hypothesis. We model the merozoite as a hard egg-shaped particle and the erythrocytes using a continuum membrane model [1, 2]. Typical snapshot from computer simulations is shown in Figure 1. In this talk, I will discuss the role of erythrocyte deformability and parasite-membrane adhesion in the alignment process using multiscale modeling. We show that parasite-membrane interactions with an inhomogeneous contact interaction that describes an adhesion-strength gradient on the parasite plasma membrane lead to much faster alignment compared with experimentally measured timescales; pure rotational diffusion of the parasite leads to too slow alignment [3]. Therefore, we simulate the adhesion without a gradient but considering receptor-ligand bond dynamics [4]. I will show how the shape fluctuations and deformability of the erythrocytes along with the stochastic nature of receptor-ligand bond formation predict alignment times that are consistent with experimental observations. I will also discuss the role of parasite shape in the alignment process and show that original shape of the parasite performs better compared other shapes at various conditions [5]. Finally, I will provide an update on and outlook for our project on Toxoplasma gondii invasion into host cells within the SPP 2332 "Physics of Parasitism".
References:
[1] Fedosov, Dmitry, et al. "A multiscale red blood cell model with accurate mechanics, rheology, and dynamics." Biophysical journal 98.10 (2010): 2215-2225.
[2] Dasgupta, Sabyasachi, et al. "Membrane-wrapping contributions to malaria parasite invasion of the human erythrocyte." Biophysical journal 107.1 (2014): 43-54.
[3] Hillringhaus, Sebastian, et al. "Importance of erythrocyte deformability for the alignment of malaria parasite upon invasion." Biophysical journal 117.7 (2019): 1202-1214.
[4] Hillringhaus, Sebastian, et al. "Stochastic bond dynamics facilitates alignment of malaria parasite at erythrocyte membrane upon invasion." Elife 9 (2020): e56500.
[5] Dasanna, Anil K., et al. "Effect of malaria parasite shape on its alignment at erythrocyte membrane." Elife 10 (2021): e68818.