%0 Generic %A Fröhlich, Benjamin %D 2019 %F heidok:26533 %R 10.11588/heidok.00026533 %T Haemoglobinopathies and the Protection Against Severe Malaria: Probing Cytoadhesion and Mechanics of Plasmodium falciparum Infected Erythrocytes %U https://archiv.ub.uni-heidelberg.de/volltextserver/26533/ %X Haemoglobinopathies and the Protection Against Severe Malaria: Probing Cytoadhesion and Mechanics of Plasmodium falciparum Infected Erythrocytes Aim of this thesis was the probing of the cytoadhesion and the mechanical properties of Plasmodium falciparum infected human wildtype and haemoglobinopathic erythrocytes, to shed light on the protection mechanism against severe malaria associated with haemoglobin polymorphisms. In Chapter 3, the cytoadhesion of infected wildtype and haemoglobinopathic erythrocytes was probed using solid-supported lipid bilayers functionalized with CD36 or ICAM-1, acting as in vitro endothelial cell membrane models. Under static conditions, the binding strength was quantified in terms of the critical pressure of detachment based on cell detachment by laser induced pressure waves. Additionally, the number of binding events and the critical shear stress of detachment were determined based on classical parallel plate flow experiments at physiological relevant shear stresses. Furthermore, the shear stress dependent changes in tight adhesion area were investigated based on label-free reflection interference contrast microscopy. In Chapter 4, the parasite induced changes to the erythrocyte mechanics were probed at different parasite stages using label and contact-free flicker spectroscopy, yielding the membrane bending modulus, the membrane tension, the harmonic membrane confinement by the cytoskeleton and the apparent cytosolic viscosity. Moreover, a comprehensive image of the intraerythrocytic parasite metabolism was generated using quantitative scanning X-ray fluorescence microscopy.