N-STEAROYL-PHOSPHATIDYLSERINE - SYNTHESIS AND ROLE IN DIVALENT-CATION-INDUCED AGGREGATION AND FUSION

N-Acylphosphatidylserines have been isolated from intact and injured t issues, but the participation of such acidic phospholipids in membrane aggregation and fusion has not been demonstrated. We have synthesized N-stearoylphosphatidylserine (NSPS) and examined divalent-cation-indu ced aggregation of NSPS-liposomes, which leads to membrane destabiliza tion and fusion. The purified lipid was characterized by its chromatog raphic and spectroscopic (infrared and H-1 nuclear magnetic resonance) properties and by its chemical degradation pattern. Aggregation of un ilamellar NSPS-liposomes was studied as a function of calcium and magn esium concentration. The ability of calcium and magnesium to induce ve sicle aggregation is higher for phosphatidylserine (PS)-liposomes (thr eshold concentration 1.5 mM for calcium and 4.6 mM for magnesium) than for NSPS-liposomes (threshold concentration 2.8 mM for calcium and 6. 6 mM for magnesium). The irreversibility of the aggregation reactions after adding EDTA suggests that vesicle fusion might occur in the pres ence of calcium and magnesium. Preliminary studies, based on mixing of both lipid and internal aqueous contents, show that fusion rather tha n aggregation of NSPS-liposomes occurs in the presence of calcium ions . The tendency of NSPS-liposomes to aggregate at higher cation concent rations than PS-liposomes suggests that N-acylation of phosphatidylser ine protects the membrane against degenerative damage caused by aggreg ation and fusion.