Computational study on the uptake of soft nanoparticles and nanoparticle cluster by cells

Abstract

Nanoparticles (NPs) and exosomes used to transport therapeutic drug molecules to cells have attracted considerable attention in biopharmaceuticals. However, soft NPs entering cells with different angles are hard to be simulated by traditional theoretical endocytic models, let alone clustering of NPs with varied shapes. Here, the endocytic model based on the co-rotational grid method is implemented. The endocytosis of a single soft NP and a nanoparticle cluster (NPC) are investigated. Both the actin force and the dynamic assembly of the clathrin coat have been considered. The results show that NP size is the main factor affecting the internalization efficiency, followed by the aspect ratio, and finally the entry angle. The increase in NP size, aspect ratio, and entry angle will lead to a decrease in internalization efficiency. However, the final configuration of the endocytic vesicle and the internalization efficiency are both independent of the entry angle for NPs with an equivalent radius greater than 15 nm. Besides, a large entry angle can assist a large soft NP in successfully entering cells. The increase in NP stiffness also reduces the internalization efficiency considering the actin force required during endocytosis. The transformation of the NP from the inclined configuration to the vertical configuration is mainly due to NP deformation. Compared with a single NP, NPC has a lower internalization efficiency. The results provide new mechanistic insights into the endocytosis of soft NPs and NPCs.