Exchangeable Mimics of DPPC and DPPG Exhibiting Similar Nearest-Neighbor Interactions in Fluid Bilayers

The interactions between an exchangeable mimic of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), Phos(±), with an exchangeable mimic of cholesterol, Chol, have been analyzed in fluid bilayers by means of nearest-neighbor recognition measurements. These interactions have been found to be very similar to those of an exchangeable mimic of 1,2-dipalmitoyl-sn-glycerol-3-phospho-(1′rac-glycerol) (DPPG), Phos(−), interacting with Chol. Thus, both phospholipids have a similar preference for becoming nearest-neighbors of Chol in the liquid-ordered (l₀) phase, and both mix, ideally, with Chol in the liquid-disordered (l_d) phase. These findings, together with the almost negligible screening effects found for the latter, provide strong evidence that electrostatic forces play a minor role in the preference that both phospholipids have in becoming a favored nearest-neighbor of Chol. They also imply that the main driving force for forming the liquid-ordered phase, and for defining the lateral organization of this phase, is an intrinsic affinity that high-melting lipids and cholesterol have for each other.