Collective Behavior of Silica Nanoparticle Assemblies Governs Translocation Across Pulmonary Surfactant: From...

The expanding biomedical applications of nanomaterials have raised concerns about their inhalation toxicity. Nanoparticle (NP) interactions with the pulmonary surfactant (PS) monolayer are central to understanding this risk. Despite extensive knowledge of the interaction mechanisms between a single NP and the PS monolayer, the synergistic effects of multiple NPs on their translocation remain poorly understood. Here, coarse-grained molecular dynamics simulations were employed to systematically explore the translocation characteristics of silica nanoparticles (SiO₂NPs)─varying in size (2, 4, 6, and 8 nm), morphological complexity (spherical and cubic), and arrangement (linear and matrix)─across the PS monolayer, as well as their impacts on PS monolayer structure. The results show that (1) Morphological synergy─an increasing proportion of cubic SiO₂NPs enhances the inter-NP aggregation but reduces overall penetration ability. (2) Architectural damage signatures─matrix arrangement causes more significant damage to the PS monolayer compared to the linear arrangement, primarily manifesting as partial structural disorder and channel formation, whereas the linear arrangement is more likely to cause changes in monolayer curvature. (3) Critical size window phenomenon─two critical thresholds (α: 4-6 nm; β: 6-8 nm) define a maximum disruption zone where same-sized NP groups exert peak destabilizing effects on PS integrity. (4) Size hierarchy dominance─in SiO₂NP groups with large size disparity, larger SiO₂NPs dominate the overall behavior and significantly inhibit monolayer penetration. This work provides a systematic simulation framework for relating multi-NP architecture to translocation and PS disruption and may help generate testable hypotheses to guide future inhalation toxicology studies and nanomaterial research.