Structure and dynamics of liposomes designed for drug delivery: coarse-grained molecular dynamics simulations to reveal the role of lipopolymer incorporation

In this work, coarse-grained molecular dynamics simulations are carried out in NPTH and NVTE statistical ensembles in order to study the structure and dynamics properties of liposomes coated with polyethylene glycol (PEG). The considered liposomes are made by membrane bilayer DPPC with DPPC-PEG incorporated lipopolymers, in an aqueous environment. We have described the two essential PEG conformation regimes, mushroom and brush, and their properties which depend on the grafting density. The effects of grafting density on the structure and dynamics of the membrane were also studied. Our simulations were then discussed by comparing with the available experimental results and by referring to the suitable theoretical models. The results from the NPTH simulations agree with the experimental data of X-ray diffraction and with scale and mean-field theories in terms of thickness of the PEG layer and thickness of the DPPC bilayer membrane. The results from NVTE simulations are found in good agreement with the experimental results from studying the diffusion of the DPPC bilayer membrane and the PEG. The analysis of the mean square displacement revealed that the dynamics of the membranes in the plane show a subdiffusion due to the cage effect and that the grafted PEG dynamics is better described by the Rouse diffusion-mode. Thus, from a macroscopic viewpoint, the incorporation of DPPC-PEG plays an important role in the protection and lubrication of the liposome.