Divalent cation-dependent interaction of sulfated polysaccharides with phosphatidylcholine and mixed phosphatidylcholine/phosphatidylglycerol liposomes.

The Ca(2+)-dependent interaction of various polyanionic polysaccharides (chondroitin sulfate, heparin, dextran sulfate, beta-cyclodextrin sulfate, hyaluronic acid and carboxymethyldextran) with multilamellar dimyristoyl phosphatidylcholine (DMPC) liposomes was investigated by calorimetric and fluorescence spectroscopic measurements. It was found that an observed polysaccharide-induced phospholipid phase separation depends on the density of the sulfate groups along the polysaccharide chain independent of the presence of additional carboxyl groups. The phase separation resulting from the drastic dehydration of the covered membrane regions is monitored by the upward shift of the lipid phase transition and by the blue shift of the emission spectrum of a headgroup-dansylated phosphatidylethanolamine (DPE). This shift is only observable if the required polysaccharide chain length contains at least three glycosyl units. The Ca(2+)-mediated interaction of dextran sulfate with various phosphatidylcholines, differing in their compressibility, showed the maximal difference between the phase transition temperatures of the lipid phase covered by the polysaccharide and the uneffected lipid domains for dielaidinoyl phosphatidylcholine (DEPC), the most compressible phospholipid investigated here. Mixed negatively charged DMPC/dimyristoyl phosphatidylglycerol (DMPG) liposomes were found to compete with the likewise negatively charged dextran sulfate for the binding of Ca2+. At excess Ca2+ concentrations, the binding of the polysaccharide was strengthened, compared to pure DMPC liposomes. The monovalent cation sodium, was able to inhibit the interaction between the membrane surface and dextran sulfate. Various divalent cations were found to mediate the interaction, depending on their ionic radii and electron configuration. Within the second group of the periodic system Ca2+ is the most effective ion. However, within the horizontal forth period the ability to bind sulfated dextran to membrane surfaces decreases from Ca2+ to Ni2+, but then increases again if Cu2+ or Zn2+ was used as the mediating ion.