The Interaction of Human Serum Albumin with Dioctanoylphosphatidylcholine in Aqueous Solutions

The interaction between human serum albumin (HSA) and the short-chain phospholipid dioctanoylphosphatidylcholine (diC 8 PC) in aqueous solutions at pH 3.2, 7.4, and 10.0 at high and low ionic strength has been investigated. Static and dynamic light scattering methods have shown that the HSA is partially associated in these aqueous solutions with an association number of 1.67 ± 0.02. On the addition of phospholipid up to a concentration equal to its critical micellar concentration (cmc) the association increases, and at high ionic strength (0.188 M) at pH 3.2 and 7.4 the HSA is largely dimeric with a small proportion of trimeric and possibly more associated species. The interaction can be followed using laser Döppler velocimetry to measure the ζ potentials of HSA in the presence of diC 8 PC. At pH 3.2 where both HSA and diC 8 PC are positively charged, the interaction results in a marked decrease in ζ potential as the cmc of the PC is approached. At pH 10.0 where HSA is negatively charged and diC 8 PC is zwitterionic, the ζ potentials become less negative as the cmc is approached. Microcalorimetry measurements of the interactions at pH 3.2 and 7.4 suggest that after the initial interaction between dimeric HSA and diC 8 PC, further interaction involves the exothermic partial dissociation of dimeric HSA and the interaction between monomeric HSA with HSA−diC 8 PC complexes.