Investigation of phospholipid area compression induced by calcium-mediateddextran sulfate interaction

The association of anionic polyelectrolytes such as dextran sulfate (DS) to zwitterionic phospholipid surfaces via Ca2+ bridges results in a perturbat ion of lipid packing at physiologically relevant Ca2+ concentrations. Lipid area compression was investigated in 1,2-dimyristoyl-sn-glycero-3-phosphoc holine (DMPC) multilamellar bilayer dispersions by H-2-NMR and in monolayer studies. Binding of DS to DMPC surfaces via Ca2+ results in denser lipid p acking, as indicated by higher lipid chain order. DMPC order parameters are homogeneously increased throughout the lipid bilayer. Higher order transla tes into more extended hydrocarbon chains and decreased average lipid area per molecule. Area compression is reported as a function of DS concentratio n and molecular weight. Altering the NaCl and Ca2+ concentrations modified electrostatic interactions between DS and phospholipid. A maximal area redu ction of Delta A = 2.7 Angstrom(2) per DMPC molecule is observed. The lipid main-phase transition temperature increases upon formation of DMPC/Ca2+/DS -complexes. Lipid area compression after addition of DS and Ca2+ to the sub phase was also observed in monolayer experiments. A decrease in surface ten sion of up to 3.5 mN/m at constant molecular area was observed. DS binds to the lipid headgroups by formation of Ca2+ bridges without penetrating the hydrophobic region. We suggest that area compression is the result of an at tractive electrostatic interaction between neighboring lipid molecules indu ced by high local Ca2+ concentration due to the presence of DS. X-ray diffr action experiments demonstrate that DS binding to apposing bilayers reduces bilayer separation. We speculate that DS binding alters the phase state of low-density lipoproteins that associate with polyelectrolytes of the arter ial connective tissue in the early stages of arteriosclerosis.