The Effect of an Integral Membrane Protein on Lipid Polymorphism in the Cardiolipin‐Ca2+ System

Abstract
The addition of Ca2+ to aqueous dispersions of cardiolipin triggers complete hexagonal (HII) phase formation at Ca2+/cardiolipin molar ratios ≥ 1.0 as detected by 31P NMR and freeze‐fracture electron microscopy. Incorporation of the integral membrane protein glycophorin prevents the bilayer → hexagonal (HII) phase transition at Ca2+/cardiolipin ratios as high as 15:1. Removal of the outwardly oriented, negatively charged sialic‐acid‐containing sugar groups of glycophorin with trypsin had little effect on the bilayer‐stabilizing capacity of the protein. As the Ca2+ binding was found to be similar in both the cardiolipin and the cardiolipin‐glycophorin systems, it can be concluded that the protein exerts a bilayer‐stabilizing effect on the cardiolipin. In addition, the possibility that glycophorin may prevent vesicle fusion is also discussed.

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