(316e) Influence of Silica Nanoparticle Hydrophobicity on the Interfacial Dynamics of DPPC Monolayers

The pulmonary surfactant, a mixture of various amphiphilic compounds, forms a critical interface at the alveolar air-liquid boundary in the lungs. Dipalmitoylphosphatidylcholine (DPPC) constitutes the primary phospholipid component, accounting for approximately 65% of the total phospholipid content, and plays a pivotal role in maintaining low surface tension levels essential for efficient respiratory function. As the development and utilization of nanoparticles continue to expand, the inevitable release of these nanomaterials into the environment raises concerns regarding their potential impact on pulmonary health. Elucidating the fundamental interfacial behavior of DPPC and the consequences of nanoparticle incorporation into the DPPC monolayer is crucial for understanding the implications of ultrafine particulates in the alveolar environment. In this study, we employed hydrophilic, hydrophobic, and amphiphilic silica nanoparticles (SNPs) as model systems for engineered nanoparticles (ENPs). Monodispersed 50 nm silica nanoparticles were synthesized, and their surface chemistry was modulated through functionalization with chlorotrimethylsilane to impart varying degrees of hydrophobicity. Utilizing a Langmuir-trough apparatus to simulate the alveolar air-water interface, mixed DPPC/SNP monolayers were formed, and their interfacial behavior was characterized through surface pressure-area isotherms and dilational rheology measurements, complemented by simultaneous fluorescence imaging for structural and thermodynamic analysis. Our studies demonstrated that the surface hydrophobicity of the nanoparticles exerts a strong influence on the intermolecular interactions and phase behavior of the DPPC monolayer. Hydrophobic SNPs were found to intercalate into the hydrophobic acyl chain region of the DPPC molecules, leading to a condensation effect and enhanced packing density. This interaction was attributed to the favorable van der Waals forces between the hydrophobic nanoparticle surface and the hydrocarbon chains of DPPC. In contrast, hydrophilic SNPs exhibited a tendency to reside in the hydrophilic headgroup region of the monolayer, resulting in a more expanded phase and reduced packing efficiency. Amphiphilic SNPs displayed intermediate behavior, with their orientation and distribution within the monolayer governed by the balance of hydrophobic and hydrophilic interactions. The changed packing arrangement and intermolecular forces within the DPPC monolayer, induced by the presence of SNPs, were reflected in the surface pressure-area isotherms and viscoelastic properties obtained from dilational rheology measurements. The presence of hydrophobic SNPs led to an increase in the maximum surface pressure and a reduction in the mean molecular area, indicative of enhanced intermolecular cohesion. Conversely, hydrophilic SNPs caused a decrease in surface pressure and an expansion of the mean molecular area, suggesting a disruption of the orderly packing of DPPC molecules. Amphiphilic SNPs exhibited intermediate effects, contingent upon the relative proportions of hydrophobic and hydrophilic groups on their surface. These findings underline the major role of nanoparticle surface chemistry in dictating the interfacial behavior and stability of DPPC monolayers. The insights gained from this biophysical and interfacial science investigation not only advance our understanding of the fate and potential toxicity of inhaled ENPs but also inform the rational design of nanomaterial-based drug delivery systems targeting the pulmonary route.