**8. Beyond Experiments: Exploiting Computational Tools for Elucidating the Interaction of Lung Surfactant with Inhaled Particles**

The use of computational tools for the evaluation of the interaction of particles with LS is rare due to the complexity of these types of systems, which require a strong computational effort. However, some studies have evidenced that molecular dynamic simulations can help the understanding of the dynamics of the composition remodeling process, and how this is modified by the incorporation of particles [86].

Hu et al. [19] demonstrated, by using coarse-grained molecular dynamics, the differences in the translocation pathway of hydrophilic and hydrophobic particles, which agrees with experimental results. Thus, hydrophilic particles undergo an easy translocation through the LS films upon compression, whereas hydrophobic particles were retained within the LS layer. This different behavior was found to be the result of the different abilities of particles for the binding of the surface-active material, with the binding of SP-B being essential for the clearance of hydrophilic particles.

The interaction of hydrophobic carbonaceous particles with LS films has also been explored by using molecular dynamics, which has shown the direct interaction of such particles with the surfactant proteins, altering the interfacial organization of the LS film. Furthermore, the simulations evidence that asymmetric particles are placed at the interface under compression in a direction perpendicular to the monolayer [241,242], which agrees with the experimental picture found for the interaction of graphene nanosheets and LS model films [129,243]. On the other side, molecular dynamic simulations have provided additional evidences on the dose-dependent inhibition of the LS performance upon the deposition of carbonaceous particles [244], which agrees with the experimental findings [63,118,129].

Molecular dynamic simulations were also used for confirming that particles alter the exchange of material between the interface and the adjacent fluid subphase, which plays a critical role in the LS functioning [164]. This agrees with the molecular dynamic simulations by Li et al. [245] which evidenced that the transport of particles to the LS film can disrupt the ultrastructure and fluidity of the interface, resulting in a premature alveolar collapse.
