DIVALENT CATION-DEPENDENT INTERACTION OF SULFATED POLYSACCHARIDES WITH PHOSPHATIDYLCHOLINE AND MIXED PHOSPHATIDYLCHOLINE PHOSPHATIDYLGLYCEROL LIPOSOMES

The Ca2+-dependent interaction of various polyanionic polysaccharides (chondroitin sulfate, heparin, dextran sulfate, beta-cyclodextrin sulf ate, hyaluronic acid and carboxymethyldextran) with multilamellar dimy ristoyl phosphatidylcholine (DMPC) liposomes was investigated by calor imetric and fluorescence spectroscopic measurements. It was found that an observed polysaccharide-induced phospholipid phase separation depe nds on the density of the sulfate groups along the polysaccharide chai n independent of the presence of additional carboxyl groups. The phase separation resulting from the drastic dehydration of the covered memb rane regions is monitored by the upward shift of the lipid phase trans ition and by the blue shift of the emission spectrum of a headgroup-da nsylated phosphatidylethanolamine (DPE). This shift is only observable if the required polysaccharide chain length contains at least three g lycosyl units. The Ca2+-mediated interaction of dextran sulfate with v arious phosphatidylcholines, differing in their compressibility, showe d 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 compres sible phospholipid investigated here. Mixed negatively charged DMPC/di myristoyl phosphatidylglycerol (DMPG) liposomes were found to compete with the likewise negatively charged dextran sulfate for the binding o f Ca2+. At excess Ca2+ concentrations, the binding of the polysacchari de was strengthened, compared to pure DMPC liposomes. The monovalent c ation sodium, was able to inhibit the interaction between the membrane surface and dextran sulfate. Various divalent cations were found to m ediate the interaction, depending on their ionic radii and electron co nfiguration. Within the second group of the periodic system Ca2+ is th e most effective ion. However, within the horizontal forth period the ability to bind sulfated dextran to membrane surfaces decreases from C a2+ to Ni2+, but then increases again if Cu2+ or Zn2+ was used as the mediating ion.