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.
The cytotoxicity of nanoparticles (NPs) and their potential applications in drug delivery and intracellular imaging have been extensively investigated, and a thorough molecular understanding of how cellular membrane responds to the introduction of NPs is essential for biomaterial design. In this work, N-varied dissipative particle dynamics (DPD) simulation is applied to investigate how a membrane responds to adsorption of ligand-coated NP. Depending on the membrane surface tension, ligand area density and NP size, four kinds of membrane responses are observed: membrane rupture, NP adhesion, NP penetration, and receptor-mediated endocytosis. While endocytosis provides an effective pathway for cellular uptake of NPs, the NP penetration and NP-induced membrane rupture are related to cytotoxicity. These results support the recent experimental reports that NPs have a Janus face for their biomedical applications: serving as carriers for the transmembrane transport of drug and causing cytotoxicity.
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