Lateral heterogeneity in fluid bilayers composed of saturated and unsaturated phospholipids

Evidence has been obtained for the existence of lateral heterogeneity in fluid bilayers composed of mixtures of saturated and unsaturated phospholipids by use of nearest-neighbor recognition (NNR) methods [Vigmond, S. J.; Dewa, T.; Regen, S. L. J. Am. Chem. Sec., 1995, 117, 7838]. Disulfide-based dimers were synthesized from a homologous series of saturated phosphoethanolamines (PEs) and analogous PEs bearing one or two double bonds and were chemically equilibrated in the bilayer state via thiolate-disulfide interchange reactions. The magnitude of NNR that was observed in these systems (i.e., the thermodynamic preference for homodimer formation) was found to correlate with the difference between the gel-to-liquid crystalline phase transition temperatures of the homodimers that were present; the larger the difference, the greater the recognition. Inclusion of 40 mol % of cholesterol had very little influence on the extent of NNR. Dilution of two membranes that showed the largest extent of recognition, with a nonexchangable phospholipid (1,2-dimyristoyl-sn-glycero-3-phosphocholine), resulted in a significant reduction in NNR. These results provide compelling evidence for the existence of lateral heterogeneity in the absence of this diluent. The implications of these findings, with respect to the two-dimensional structure of biological membranes, are briefly discussed.