Membrane-mediated precipitation of calcium phosphate in model liposomes with matrix vesicle-like lipid composition

The present study examined calcium phosphate precipitation in aqueous suspensions of artificial liposomes which closely resembled matrix vesicles (MV) in membrane lipid composition. At 22 degrees C, the liposomes per se did not initiate precipitation in the suspending medium for up to 120 h when the latter was made supersaturated with respect to hydroxyapatite (2.25 mM Ca2+, 1.5 mM PO4, 240 mosmol, pH 7.4). Likewise, the suspending medium remained stable for up to 72 h when precipitation was induced within the aqueous interiors of the liposomes by encapsulating pH 7.4-buffered 50 mM PO4 solutions in the interior spaces and making the enclosing membranes permeable to external solution Ca2+ ions with the ionophore X-537A. However, extraliposomal precipitation readily occurred under these latter conditions when phosphatidylserine (PS) and sphingomyelin (Sph) were deleted from the MV-like lipid formulation used to prepare the liposomes. These results suggest that lipidic membrane constituents such as PS and Sph may have a controlling influence on MV-mediated calcification in vivo by affecting the release of intravesicularly formed mineral crystals into the extracellular matrix space where they can subsequently grow and proliferate.