Nanoparticle (NP) cytotoxicity assessment requires a thorough understanding of the mechanisms by which they interact with the cell membrane. In this study, extensive Coarse-Grained Molecular Dynamics simulations are performed to investigate the partitioning of an anionic, ligand-decorated NP in model membranes containing DPPC phospholipids and different concentrations of cholesterol. 5-µs unbiased MD simulations with the NP inserted in the bilayer core reveal that the hydrophobic and hydrophilic ligands of the NP surface rearrange to form optimal contacts with the lipid bilayer, leading to the so-called “snorkeling effect”. Inside cholesterol-containing bilayers, the NP induces rearrangement of the structure of the lipid bilayer in its vicinity from the liquid-ordered to the liquid phase spanning a distance almost twice its core radius. Based on the physical insights obtained in this study, we propose a mechanism of cellular anionic NP partitioning, and conclude that the translocation of anionic NPs through cholesterol-rich membranes must be accompanied by formation of cholesterol-lean regions in the proximity of NPs. When several anionic NPs are embedded in the model membrane, the self-assemble to form linear clusters, or chains, which were later confirmed experimentally through Cryo-TEM. We analyze the driving forces for this self-assembly and offer an explanation based on the recently discovered orderphobic effect. Finally, we present a web-based server that we created for the construction of NPs of any type, size, and shape, and composition. The research leading to these results has been co-funded by the European Commission under the H2020 Research Infrastructures contract no.675121 (project VI-SEEM).

Investigating nanoparticle self-assembly at the nano-membrane interface

255th National Meeting (2018)

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