INFLUENCE OF HEAD GROUP MISMATCH ON THE MISCIBILITY OF PHOSPHOLIPIDS IN THE PHYSIOLOGICALLY-RELEVANT FLUID-PHASE - A NEAREST-NEIGHBOR RECOGNITION ANALYSIS

The mixing behavior of phosphoethanolamine (PE)-like and phosphoglycer ol (PG)-like lipids have been examined in the fluid bilayer state by u se of nearest-neighbor recognition methods [Vigmond, S.J; Dewa, T.; Re gen, S. L. J. Am. Chem. Soc. 1995, 117, 7838]. Disulfide-based phospho lipid dimers derived from 1,2-dimyristoyl-sn-glycero-3-phosphoethanola mine (DMPE) have been synthesized, containing PB and PG-like head grou ps. Subsequent exchange and equilibration of the monomer units, via th iolats-disulfide interchange, produced a nonstatistical distribution o f dimers in the fluid bilayer phase (60 degrees C); i.e., heterodimer/ homodimer ratio of 1.76 +/- 0.05 was formed. Analogous membranes that were rich in cholesterol (i.e., 29 mol %) produced a. statistical mixt ure of dimers. Equilibration experiments that were carried out using P E-like and PG-like lipids derived from 1,2-dipalmitoyl-sn-glycero-3-ph osphoethanolamine (DPPE) and DMPE, respectively, gave similar results, except that a greater level of nearest-neighbor recognition was evide nt in the absence of cholesterol. The biological implications of these findings are briefly discussed.