<i>In Silico</i> Study of Gold Nanoparticle Uptake into a Mammalian Cell: Interplay of Size, Shape, Surface Charge, and Aggregation

The study of interactions between Au nanostructures and living cells is a fundamental aspect that can be applied for promising applications in nanomedicine. In the present work, we performed coarse-grained molecular dynamics (MD) simulations to observe the internalization pathways of Au nanostructures (nanospheres, nanocages, nanorods, nanoplates, and nanohexapods) into an idealized mammalian plasma membrane at an unprecedented level of complexity. Compared with a simple lipid bilayer model consisting of two lipid species, the different cellular uptake pathways of the gold nanoparticle (AuNP) were found. We highlight that the complexity of the lipid bilayer models plays an important role in the uptake pathway of nanoparticles (NPs). The permeability of aggregated AuNPs was much less than the NP counterpart. Spherical AuNPs showed pronounced size and surface charge dependence in their translocation through the plasma membrane. The translocation rates of different Au nanostructures were also evaluated, and we found that the Au nanohexapod exhibited highest cellular uptake. Understanding the interrelationship between size, shape, surface charge, and aggregation of Au nanostructures provides a clear view on the design of Au nanostructures for developing new diagnostic strategies and drug delivery