The interplay between surface-functionalized gold nanoparticles and negatively charged lipid vesicles.

The comprehensive understanding of the interactions between gold nanoparticles (AuNPs) and phospholipid vesicles has important implications in various biomedical applications; however, this is not yet well understood. Here, coarse-grained molecular dynamics (CGMD) simulations were performed to study the interactions between functionalized AuNPs and negatively charged lipid vesicles, and the effects of the surface chemistry and surface charge density (SCD) of AuNPs were analyzed. It is revealed that AuNPs with different surface ligands adhere to the membrane surface (anionic AuNPs) or get into the vesicle bilayer (hydrophobic and cationic AuNPs). Due to the loose arrangement of lipid molecules, AuNPs penetrate curved vesicle membranes more easily than planar lipid bilayers. Cationic AuNPs present three different interaction modes with the vesicle, namely insertion, partial penetration and complete penetration, which are decided by the SCD difference. Both hydrophobic interaction and electrostatic interaction play crucial roles in the interplay between cationic AuNPs and lipid vesicles. For the cationic AuNP with a low SCD, it gets into the lipid bilayer without membrane damage through the hydrophobic interaction, and it is finally stabilized in the hydrophobic interior of the vesicle membrane in a thermodynamically stable "snorkeling" configuration. For the cationic AuNP with a high SCD, it crosses the vesicle membrane and gets into the vesicle core through a membrane pore induced by strong electrostatic interaction. In this process, the membrane structure is destroyed. These findings provide a molecular-level understanding of the interplay between AuNPs and lipid vesicles, which may further expand the application of functional AuNPs in modern biomedicine.