Yes / Lung surfactant (LS) monolayers that continuously expand and compress during breathing cycles, act as the first line barrier for inhaled nanoparticles. It is known that nanoparticles which adsorb to the surface of the surfactant layer facilitate the rearrangement of lipids and peptides at various stages of the breathing cycle. However, the structural mechanisms for this ability of the lipid rearrangement are not yet fully understood. Coarse-grained molecular dynamics simulations are performed to investigate the role of surfactant protein B (SP-B) segments (SP-B1–25) in modulating the biophysical properties of the surfactant monolayer in the presence of polydisperse gold nanoparticles (AuNPs) at different concentrations. Herein, we observe that the AuNPs significantly alter the inherent structural and dynamical properties of the monolayer and its components in three different breathing states. When adsorbed into the monolayer, the AuNPs inhibit the ability of the monolayer to recover its surface tension and other properties. The presence of SP-B1–25 in the monolayer accelerates the diffusion of the monolayer phospholipids, contrarily to the role of AuNPs on phospholipid diffusion. Also, the AuNPs and the peptides in the monolayer significantly increase their agglomeration in the presence of one another. Overall, the simulations predict that the presence of polydisperse AuNPs hampers the stability and biophysical functions of the LS in contrast to the role of the peptide. This study provides a clear view of the hydrophobic peptide role in the LS monolayer at the interface along with the interactions and the translocation of AuNPs that could have a significant impact to assess the NPs inhalation. / This work was completed with the support of University of Technology Sydney (UTS) FEIT Research Scholarship, UTS IRS (S. I. H.).