Molecular understanding of receptor-mediated membrane responses to ligand-coated nanoparticles

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.