TY  - GEN
CY  - Heidelberg
A1  - Jäger, Julia
Y1  - 2020///
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/28421/
N2  - Red blood cells (RBCs) are the type of human cells that are most accessible to biophysical multiscale modelling because they feature a regular molecular cell envelope organization and lack internal organelles. Extensive previous research on how their physical properties are shaped by the actin-spectrin network and other molecular constituents provides a good basis to understand the physical consequences of  becoming infected by malaria parasites, which use RBCs to hide from the immune system. After invasion, the malaria parasite rebuilds the RBC-envelope, relying on the self-assembly of parasite proteins released into the cytoplasm. Optical tweezer experiments have shown that infected RBCs (iRBCs) become stiffer. Here, the underlying mechanisms are investigated by quantitative analysis of the flickering spectrum of iRBCs. Extending the membrane Hamiltonian by anchoring points, we find that the parasite stiffens the membrane mostly by introducing more connections between the lipid bilayer and the underlying cytoskeleton. To identify the exact points of attack in the RBC-cytoskeleton,
a reaction-diffusion model is developed to investigate the dynamical equilibrium of the RBC-cytoskeleton, allowing us to simulate different scenarios of parasite protein
self-assembly and to compare these results with experimental data. The parasite induces protrusions to make the iRBC adhesive, thus increasing residence time in the vasculature and avoiding clearance by the spleen. The number of new transmembrane receptors incorporated into the cell membrane is estimated by quantitative analysis of fluorescence and electron microscopy data. We develop a finite element model  aiming to predict the effect of these changes on the movement of iRBCs in hydrodynamic flow. Finally, as an instructive contrast to RBC-mechanics, we
investigate the spreading of tissue cells onto micropatterned substrates leading to a complete change in their actin cytoskeleton. A Cellular Potts Model is used to describe this highly dynamic situation. We find that due to its focus on geometrical aspects, it predicts reliably how a family of actin stress fibres is formed, which serves as memory of the spreading process.
TI  - Multiscale Modelling of Malaria-Infected Red Blood Cells
AV  - public
ID  - heidok28421
ER  -