Receptor-Mediated Endocytosis of Nanoparticles: Roles of Shapes, Orientations, and Rotations of Nanoparticles.

A complete understanding of the interactions between nanoparticles (NPs) and the cell membrane is essential for the potential biomedical applications of NPs. The rotation of the NP during the cellular wrapping process is of great biological significance and has been widely observed in experiments and simulations. However, the underlying mechanisms of the rotation and their potential influences on the wrapping behavior are far from being fully understood. Here, by coupling the rotation of the NP with the diffusion of the receptors, we set up a model to theoretically investigate the wrapping pathway and the internalization rate of the rotatable NP in the receptor-mediated endocytosis. Based on this model, it is found that the endocytosis proceeds through the symmetric-asymmetric or asymmetric-symmetric-asymmetric wrapping pathway due to the bending and membrane tension competition induced rotation of NP. In addition, we show that the wrapping rate in the direction that the wrapping proceeds can be largely accelerated by the rotation. Moreover, the time to fully wrap the NP depends not only on the size and shape of the NP but also on its rotation and initial orientation. These results reveal the roles of the shape, rotation, and initial orientation of the NP on the receptor-mediated endocytosis and may provide guidelines for the design of NP-based drug delivery systems.