Shape and stability changes in human erythrocyte membranes induced by metal cations

Asymmetric human erythrocyte ghost membranes behave as bilayer couple and exhibit a radius of curvature preference depending on the state of expansion or contraction of each side of the bilayer. The inside-out preference in the absence of added metal cations is gradually reduced as the K+ concentration is raised to 200 mM until a slight right-side-out preference may be exhibited Divalent cations (denoted 72+; Ca2+, Mg2+ and Mn2+) induce inside-out curvature at very low concentrations, right-side-out curvature at intermediate concentrations, and inside-out curvature again at high ones. This "triphasic" response is attributed to changes in the packing of acidic phospholipid (PL-) pairs in the A-face as a function of M2+ : PL- binding stoichiometry: 0 : 1 (PL- electrostatic repulsion and A-face expansion), 1 : 2 (PL2M crossbridging an contraction), and 1 : 1 (PLM+ repulsion and expansion). Generally increasing parent vesicle size is associated with higher cation concentrations. This is distinguished from the internal and external membrane blebbing preferred at different concentrations in accord with sidedness preference. Parent vesicle size was interpreted to be most closely associated with cation stabilisation (resistance to fragmentation) of the membrane, while sidedness and size (radius of curvature) of blebs were most closely correlated with packing of lipid molecules in the bilayer.