Hemoglobin S and C affect biomechanical membrane properties of P. falciparum-infected erythrocytes

During intraerythrocytic development, the human malaria parasite Plasmodium falciparum alters the mechanical deformability of its host cell. The underpinning biological processes involve gain in parasite mass, changes in the membrane protein compositions, reorganization of the cytoskeletons and its coupling to the plasma membrane, and formation of membrane protrusions, termed knobs. The hemoglobinopathies S and C are known to partially protect carriers from severe malaria, possibly through additional changes in the erythrocyte biomechanics, but a detailed quantification of cell mechanics is still missing. Here, we combined flicker spectroscopy and a mathematical model and demonstrated that knob formation strongly suppresses membrane fluctuations by increasing membrane-cytoskeleton coupling. We found that the confinement increased with hemoglobin S but decreases with hemoglobin C in spite of comparable knob densities and diameters. We further found that the membrane bending modulus strongly depends on the hemoglobinopathetic variant, suggesting increased amounts of irreversibly oxidized hemichromes bound to membranes.
Fröhlich et al. show that membrane protrusions of malaria parasite-infected blood cells reduce their membrane fluctuation due to the enforced coupling of membrane and cytoskeleton. Differential cellular mechanics of blood cells possessing variant hemoglobins that protect people from malaria suggests that oxidative stress may explain the selective advantage of certain hemoglobin variants.