Mixing behaviour of a symmetrical single-chain bolaamphiphile with phospholipids

The mixing behavior of the symmetric long-chain bolaamphiphile dotriacontane-1,1'-diyl-bis-[2-(trimethylammonio)ethylphosphate] (PC-C32-PC) with conventional phospholipids (DPPC, DMPC, and POPC) was investigated by differential scanning calorimetry and transmission electron microscopy. PC-C32-PC by itself forms nanofibers at room temperature, which convert to micellar aggregates at higher temperatures. The length of the bolaamphiphile corresponds roughly to the thickness of a lipid bilayer. However, a significant insertion of the bolaamphiphile into the phospholipid bilayer vesicles was not observed in any of the mixed systems. This is apparently due to packing problems caused by the larger space requirement of the phosphocholine headgroups of PC-C32-PC compared to the small cross-sectional area of the alkyl chain. Obviously, the insertion of these bolaamphiphiles into membrane structures with parallel oriented molecules leads to large void volumes because of this packing problem, so that the bolaamphiphiles prefer to self-assemble into fibers, where the chains can get in closer contact. On the other hand, up to a certain molar ratio, double-chain phospholipids can easily be inserted into the hydrophobic pockets of the bolaamphiphile fibers, where they stabilize the fiber structure.