Effect of Incorporation of lysolipid on the Stability of Dipalmitoyl Phosphatidylcholine Bilayer Membrane: Molecular Dynamics Simulation Approach

Abstract

Previous studies have found that incorporating monopalmitoylphosphatidylcholine(MPPC) lysolipids into PEGylated dipalmitoylphosphatidylcholines(DPPC) membranes of conventional thermosensitive liposomes lowers their phase transition temperature and promote rapid release of the encapsulated drug. Lysolipid has only one acyl chain, arranging the molecule into a conical shape with a relatively large head group compared to its single hydrocarbon tail. In this research, we present a full atomistic molecular dynamic study on the interfacial properties of the lysolipid-incorporated lipid bilayers as a function of structural variable of lipid compositions. We prepared two probable structural configurations of 10% MPPC incorporated DPPC bilayers: a ‘dispersed’ configuration of which the MPPC lipids are embedded evenly among the DPPC molecules to form a system of lipid layer that have lysolipids evenly distributed over the whole layer, and an ‘island’ configuration of which a cluster of MPPC lipids is embedded into DPPC molecules forming a island of lysolipid-agglomerate in the bilayer. Using two configurations, we analyzed how the intermolecular configuration of lysolipid-incorporated lipid bilayer affects the macroscopic properties of the bilayer between the water phases. For this purpose, the energetic profiles, density profile, and the structural correlations of the molecules where characterized for both configurations of ‘island’ and ‘dispersed’ system. The results indicate that the island system may be a promising structure for composing 10% MPPC incorporated DPPC bilayers. This study not only determines the probable structural composition of mixed MPPC/DPPC lipid bilayer but also better understands the role of the lysolipids affecting the overall behavior of the lipid bilayer.