Membrane knobs of unfixed Plasmodium falciparum infected erythrocytes: new findings as revealed by atomic force microscopy and surface potential spectroscopy.

Cerebral malaria, a severe complication of malaria, is caused by the obstruction of cerebral microvessels by Plasmodium falciparum-infected erythrocytes. Such cells adhere to endothelial cells by means of "knobs" induced on the red cell membrane by the parasites. When atomic force microscopy was used to investigate the structure of the knobs of unfixed infected red cells, each knob was found to consist of two distinct subunits, knob components that have never been seen in chemically fixed knobs examined by conventional transmission electron microscopy. Surface potential spectroscopy revealed that the knobs have a positive charge (+20 mV), whereas the remainder of the red cell plasma membrane is negatively charged. Since endothelial plasma membranes have a negative charge, the charge difference between knobs and endothelium may play a significant role in cytoadherence between the two cell types. The subunit structure of the knobs may be a steric necessity to align adherence molecules so that they can exert their effect. This study shows that the atomic force microscope has great potential for examination of cells in their native state; in combination with surface potential spectroscopy, it may uncover fundamental processes and mechanisms in cell function.