Focal erythrocyte membrane perturbations caused by nitroxide lipid analogues

Three classes of lipoidal nitroxide spin probes reversibly perturb erythrocyte membranes at low concentrations (10(-10)-10(-5) M). This is manifest in (a) decreased osmotic fragility and (b) alterations of surface topology. At bulk phase nitroxide concentrations providing maximal osmotic stabilization, the erythrocytes exhibit a classic echinocyte morphology. At nitroxide concentrations very slightly higher than those yielding minimal osmotic fragility (10(-5)-10(-4) M), the cellus undergo a sphering reaction and lyse. The morphologic sequence seen in intact cells is not observed in erythrocyte ghosts. We suggest that the spin probes initially concentrate in focal domains, which expand into echinocytic protrusions primarily due to localized weakening of membrane cohesion. We propose that cell lysis involves an irreversible breakdown in membrane domain structure.