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

Abstract

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.

Lipid/water interface of galactolipid bilayers in different lyotropic liquid-crystalline phases

“…The matrix of the mammalian plasma membrane consists primarily of glycerophospholipids (PL), i.e. phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and sphingomyelin (SM), with one saturated and the other mono-cis-unsaturated acyl chains (van Meer et al, 2008). PE together with phosphatidylglycerol are the main lipid representatives of the inner bacterial membranes (Dowhan, 1997).…”

Effects of Cholesterol on Water Permittivity of Biomimetic Ion Pair Amphiphile Bilayers: Interplay between Membrane Bending and Molecular Packing

“…Yet, the variation of ΔEbend is more dominate over the cavity effect when adding cholesterol, leading to overall increased free energy in the hydrophilic region. According to our early study on comparing IPA and phospholipid bilayers, IPA membranes have higher mechanical strength than lipid systems [18]. Hence, the effects of membrane deformation should be considered for the water permeation across most types of IPA bilayers.…”

“…In contrast, adding cholesterol into a S phase lipid bilayer disrupt the packing of nearby hydrocarbon chains. Biomimetic IPA bilayers exhibit similar phase properties to the phospholipid bilayer systems [17,18]. Also, the cholesterol additives give rise to similar effects on the IPA bilayer’s phase behavior and mechanical properties as the phospholipid bilayers [19].…”

Lipid based nanoparticles as a novel treatment modality for hepatocellular carcinoma: a comprehensive review on targeting and recent advances

“…IPAs are cheap, lipid like alternative to phospholipids [ 110 ]. They are formed of a pair of opposite charged amphiphiles [ 111 ] that can be held together through electrostatic attraction [ 112 ]. Karmakar et al prepared an IPA from an equimolar ratio of hexadecyltrimethylammonium bromide and sodium dodecyl sulphate.…”