Importance of Hydrophilic Groups on Modulating the Structural, Mechanical, and Interfacial Properties of Bilayers: A Comparative Molecular Dynamics Study of Phosphatidylcholine and Ion Pair Amphiphile Membranes.

An ion pair amphiphile (IPA), a molecular complex composed of two oppositely charged amphiphiles, is a phospholipid mimic which differs from a phospholipid only in the hydrophilic compositions. Here, we utilized molecular dynamics (MD) simulations to compare the bilayer systems composed of phosphatidylcholines (PC) and alkyltrimethylammonium-alkylsulfate IPAs with various alkyl chain lengths. The membrane properties for both liquid-disordered (Ld) and gel (S) phase bilayers were examined via running simulations above and below the main transition temperatures. The electrostatic attraction between the IPA hydrophilic groups leads to a more ordered molecular packing within both S and Ld phase IPA membranes, as revealed by the molecular area, deuterium order parameter, and gauche conformation analyses. Furthermore, IPA bilayers possess a higher area compressibility modulus, molecular tilt modulus, and effective bending rigidity than PC systems. The variation of hydrophilic groups of IPA also leads to fewer hydrogen bonds on the membrane surface and smaller electrostatic potentials for the biomimetic bilayer. The non-covalently linked head groups of IPA further decouple alkyl tilting and surface water retention. The combined results reveal the importance of hydrophilic groups of amphiphiles on modulating the membrane properties, which also provides insights for designs of biomimetic membranes.