Computational Investigations of the Interaction between the Cell Membrane and Nanoparticles Coated with a Pulmonary...

When inhaled nanoparticles (NPs) come into the deep lung, they develop a biomolecular corona by interacting with the pulmonary surfactant. The adsorption of the phospholipids and proteins gives a new biological identity to the NPs, which may alter their subsequent interactions with cells and other biological entities. Investigations of the interaction between the cell membrane and NPs coated with such a biomolecular corona are important in understanding the role of the biofluids on cellular uptake and estimating the dosing capacity and the nanotoxicology of NPs. In this paper, using dissipative particle dynamics, we investigate how the physicochemical properties of the coating pulmonary surfactant lipids and proteins affect the membrane response for inhaled NPs. We pinpoint several key factors in the endocytosis of lipid NPs, including the deformation of the coating lipids, coating lipid density, and ligand-receptor binding strength. Further studies reveal that the deformation of the coating lipids consumes energy but on the other hand promotes the coating ligands to bind with receptors more tightly. The coating lipid density controls the amount of the ligands as well as the hydrophobicity of the lipid NPs, thus affecting the endocytosis kinetics through the specific and nonspecific interactions. It is also found that the hydrophobic surfactant proteins associated with lipids can accelerate the endocytosis process of the NPs, but the endocytosis efficiency mainly depends on the density of the coating surfactant lipids. These findings can help understand how the pulmonary surfactant alters the biocompatibility of the inhaled NPs and provide some guidelines in designing an NP complex for efficient pulmonary drug delivery.