Molecular modeling of the relationship between nanoparticle shape anisotropy and endocytosis kinetics.

In this work, an N-varied dissipative particle dynamics (DPD) simulation technique is applied to investigate detailed endocytosis kinetics for ligand-coated nanoparticles with different shapes, including sphere-, rod- and disk-shaped nanoparticles. Our results indicate that the rotation of nanoparticles, which is one of the most important mechanisms for endocytosis of shaped nanoparticle, regulates the competition between ligand-receptor binding and membrane deformation. Shape anisotropy of nanoparticles divides the whole internalization process into two stages: membrane invagination and nanoparticle wrapping. Due to the strong ligand-receptor binding energy, the membrane invagination stage is featured by the rotation of nanoparticles to maximize their contact area with the membrane. While the kinetics of the wrapping stage is mainly dominated by the part of nanoparticles with the largest local mean curvature, at which the membrane is most strongly bent. Therefore, nanoparticles with various shapes display different favorable orientations for the two stages, and one or two orientation rearrangement may be required during the endocytosis process. Our simulation results also demonstrate that the shape anisotropy of nanoparticles generates a heterogeneous membrane curvature distribution and might break the symmetry of the internalization pathway, and hence induce an asymmetric endocytosis.