ROLE OF CHARGE AND HYDRATION IN EFFECTS OF POLYSIALIC ACID ON MOLECULAR-INTERACTIONS ON AND BETWEEN CELL-MEMBRANES

Previous studies have shown that the polysialic acid (PSA) moiety asso ciated with the neural cell adhesion molecule (NCAM) has strong antiad hesive properties that can influence a variety of cell-cell interactio ns. Based on the size and structure of this long linear homopolymer, w e have proposed that the activity of PSA results from its physical pro perties. In the present study, the premise that the charge and hydrati on properties of PSA underlie its effects on membrane vesicle aggregat ion is investigated through the manipulation of ionic strength. The re sults establish that the antiadhesive properties of PSA are accentuate d at low ionic strength, where charge and hydration cause expansion of the polymer size, and are absent at high ionic strengths, where the p olymer size collapses. These large effects of PSA on aggregation were shown not to result from changes in the osmolarity of the solvent or f rom the relatively small effect of ionic strength on the intrinsic fun ctional properties of the adhesion receptors. In addition to this infl uence on overall membrane-membrane interaction, PSA was found to have a highly localized and ionic strength sensitive effect on the binding of monoclonal antibodies to NCAM. Together these results suggest that the charge and hydration properties of PSA can impede both molecular i nteractions between apposing membranes and more direct contact of NCAM with other proteins at the cell surface.