Cooperative effect in receptor-mediated endocytosis of multiple nanoparticles.

The uptake of nanoparticles (NPs) by a cellular membrane is known to be NP size dependent, but the pathway and kinetics for the endocytosis of multiple NPs still remain ambiguous. With the aid of computer simulation techniques, we show that the internalization of multiple NPs is in fact a cooperative process. The cooperative effect, which in this work is interpreted as a result of membrane curvature mediated NP interaction, is found to depend on NP size, membrane tension, and NP concentration on the membranes. While small NPs generally cluster into a close packed aggregate on the membrane and internalize, as a whole, NPs with intermediate size tend to aggregate into a linear pearl-chain-like arrangement, and large NPs are apt to separate from each other and internalize independently. The cooperative wrapping process is also affected by the size difference between neighboring NPs. Depending on the size difference of neighboring NPs and inter-NP distance, four different internalization pathways, namely, synchronous internalization, asynchronous internalization, pinocytosis-like internalization, and independent internalization, are observed.