A Core-Shell Approach for Systematically Coarsening Nanoparticle-Membrane Interactions: Application to Silver Nanoparticles.

The continuous release of engineered nanomaterial (ENM) into the environment may bring about health concerns following human exposure. One important source of ENMs are silver nanoparticles (NPs) that are extensively used as anti-bacterial additives. The introduction of ENMs into the human body can occur via ingestion, skin uptake or the respiratory system. Therefore, evaluating how NPs translocate over bio-membranes is essential in assessing their primary toxicity. Unfortunately, data regarding membrane-NP interaction is still scarce, as is theoretical and in silico insight into what governs adhesion and translocation for the most relevant NPs and membranes. Coarse-grained (CG) molecular descriptions have the potential to alleviate this situation, but are hampered by the absence of a direct link to NP materials and membrane adhesion mechanisms. Here, we interrogate the relationship between the most common NP representation at the CG level and the adhesion characteristics of a model lung membrane. We find that this representation for silver NPs is non-transferable, meaning that a proper CG representation for one size is not suited for other sizes. We also identify two basic types of primary adhesion-(partial) NPs wrapping by the membrane and NP insertion into the membrane-that closely relate to the overall NP hydrophobicity and significantly differ in terms of lipid coatings. The proven non-transferability of the standard CG representation with size forms an inspiration for introducing a core-shell model even for bare NPs that are uniform in composition. Using existing all-atom molecular dynamics (MD) data as a reference, we show that this extension does allow us to reproduce size-dependent NP adhesion properties and lipid responses to NP binding at the CG level. The subsequent CGMD evaluation for 10 nm Ag NPs provides new insight into membrane binding for relevant NP sizes and into the role of water in trapping NPs into defected mixed monolayer-bilayer states. This development will be instrumental for simulating NP-membrane adhesion towards more experimentally relevant length and time scales for particular NP materials.