Study of Structural Stability and Formation Mechanisms in DSPC and DPSM Liposomes: A Coarse-grained Molecular Dynamics Simulation

Liposomes or biological vesicles can be created from cholesterol, phospholipid, and water. Their stability is affected by their phospholipid composition which can influence disease treatment and drug delivery efficacy. In this study, the effect of phospholipid type on the formation and stability of liposomes using coarse-grained molecular dynamics simulations is investigated. For this purpose, the simulation study of the DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) and DPSM (Egg sphingomyelin) lipids were considered. All simulations were carried out using the Gromacs software and Martini force field 2.2. Energy minimization (3000 steps) model, equilibrium at constant volume to adjust the temperature at 400 Kelvin and equilibrium at constant pressure to adjust the pressure, at atmospheric pressure (1 bar) have been validated. Microsecond simulations, as well as formation analysis including density, radial distribution function, and solvent accessible surface area, demonstrated spherical nanodisc structures for the DPSM and DSPC liposomes. The results revealed that due to the cylindrical geometric structure and small-size head group, the DSPC lipid maintained its perfectly spherical structure. However, the DPSM lipid showed a conical geometric structure with larger head group than other lipids, which allows the liposome to form a micelle structure. Although the DSPC and DPSM lipids used in the laboratory tests exhibit liposome and micelle behaviors, the simulation results revealed their nanodisc structures. Energy analysis including overall energy, Van der Waals interaction energy, and electrostatic interaction energy showed that DPSM liposome is more stable than DSPC liposome.