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 associated with the neural cell adhesion molecule (NCAM) has strong antiadhesive properties that can influence a variety of cell-cell interactions. Based on the size and structure of this long linear homopolymer, we have proposed that the activity of PSA results from its physical properties. In the present study, the premise that the charge and hydration properties of PSA underlie its effects on membrane vesicle aggregation is investigated through the manipulation of ionic strength. The results establish that the antiadhesive properties of PSA are accentuated at low ionic strength, where charge and hydration cause expansion of the polymer size, and are absent at high ionic strengths, where the polymer size collapses. These large effects of PSA on aggregation were shown not to result from changes in the osmolarity of the solvent or from the relatively small effect of ionic strength on the intrinsic functional properties of the adhesion receptors. In addition to this influence 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 interactions between apposing membranes and more direct contact of NCAM with other proteins at the cell surface.