(444f) Physical Mechanism of Direct Permeation of Nanoparticle across Cell Membrane

Nanoparticles (NPs) have been attracted much attention for biomedical and pharmaceutical applications. In most of the applications, NPs are required to translocate across the cell membrane and to reach the cell cytosol. Experimental studies have reported that by applying an electric field NPs can directly permeate across the cell membrane without confinement of NPs by endocytic vesicles, while damage to the cell can often be a concern. Understanding of the mechanism underlying the direct permeation of NPs under an external electric field can greatly contribute to realize a technology for the direct delivery of NPs. Here we investigated the permeation of a cationic gold NP across a phospholipid bilayer under an external electric field using a coarse-grained molecular dynamics simulation. We found that, when a specific range of electric field that is lower than the membrane breakdown intensity was applied, a unique permeation pathway was exhibited: the generated transmembrane pore immediately resealed after the direct permeation of NP. We have investigated physical mechanism of this unique direct permeation pathway by analyzing the local memebrane potential at the NP-cell membrane contact interface. Consequently, our result exibited that the the loccaly higher membrane potential at the contct interface induce spontaneous poration, resulting in the direct permeation pathway.