Role of Surface Functionalization on Cellular Uptake of AuNPs Characterized by Computational Microscopy.

A surface modification of nanoparticles (NPs) provides an effective way to control their interactions with living cells. The complete understanding of interactions between NPs and a cell membrane is a key step for the development of drug delivery. In the present work, the role of different surface charges (anionic, cationic, and zwitterionic) on the internalization through an idealized plasma membrane was investigated using a coarse-grained molecular dynamics (CGMD) technique. The decorated AuNPs used in this in silico study closely imitated those experimentally synthesized, while the idealized plasma membrane model resembled that found in living cells. The mechanism of direct translocation of a 2 nm particle by membrane was observed. The zwitterionic AuNP demonstrates a higher free-energy barrier than the positively and negatively charged AuNPs, resulting in a lack of preference for internalization across the membrane, leading to lower translocation rate and permeability of internalization. Despite the surface coverage, the agglomeration of AuNPs in a physiological condition has been observed resulting in slow unfavorable permeability. Our study highlights that in addition to surface charges, the hydrodynamic size (DH) plays an important role in the permeability of the functionalized AuNPs into the cell membrane. Through our simulations, complete understanding of interactions between ligands-coated AuNPs and the realistic plasma membrane has been established serving as a platform for the novel design of AuNPs in nanomedicine applications.