(179b) Unraveling the Role of Nanoparticle Hydrophobicity in Pulmonary Surfactant Interactions

The interfacial behavior of the pulmonary surfactant (PS) film, essential for minimizing alveolar surface tension, is dominated by dipalmitoylphosphatidylcholine (DPPC). Interactions with inhaled colloidal particles, such as engineered nanoparticles (ENPs), can compromise this function. We systematically investigated the influence of nanoparticle hydrophobicity on the phase behavior, mesoscopic structure, and interfacial rheology of DPPC monolayers at the air-water interface. Using silica nanoparticles (SNPs, 50 nm) surface-modified to tune hydrophobicity, we employed Langmuir trough techniques. Precise pressure-area isotherms quantified the thermodynamic impact of SNPs, yielding shifts in phase coexistence regions, limiting molecular areas, and isothermal compressibility , indicating altered lipid packing density and lateral interactions. Calculation of excess free energy of mixing (or related thermodynamic parameters) could further quantify DPPC-SNP affinities. Real-time epifluorescence microscopy tracked the evolution of DPPC liquid-condensed (LC) domain morphology and distribution. Hydrophilic SNPs showed interfacial activity and partitioning into the DPPC monolayer, inhibiting LC domain nucleation/growth via specific particle-lipid headgroup interactions (likely polar/electrostatic) and altering domain boundary energetics. In contrast, amphiphilic and hydrophobic SNPs demonstrated behavior governed by colloid-surface interaction principles and the hydrophobic effect, undergoing macroscopic phase separation from the DPPC film. Amphiphilic SNPs assembled into particle-rich network structures driven by interparticle forces balanced by line tension effects at the particle/lipid/water contact lines, while hydrophobic SNPs formed densely aggregated clusters due to strong interparticle van der Waals attraction minimizing water contact. Oscillatory dilational rheology measurements probed the frequency-dependent complex viscoelastic modulus, revealing distinct mechanical signatures corresponding to these nanoparticle-induced structural alterations. These findings directly link nanoparticle surface chemistry to specific intermolecular (DPPC-SNP, SNP-SNP) and colloidal forces governing nanoparticle assembly dynamics at the fluid interface and the resultant perturbation of the structure and mechanical integrity of lung surfactant layer.