Tug of War at Air-Water Interface: Understanding Lipid-Nanoparticle and Lipid-Protein Interaction Associated With Lung Surfactants at a Molecular Level

Lung surfactants [LS] are a complex mixture of lipids and proteins that line the air-water interface in the alveoli of the lungs. They lower the work of breathing by reducing the surface tension and also form a line of defense against particles small enough to enter the respiratory tract. A deficiency of LS may lead to the fatal Neonatal Respiratory Distress Syndrome [NRDS] in premature infants, whereas, an impairment may cause Acute Respiratory Distress Syndrome [ARDS], irrespective of the age. Medical intervention in the form of Surfactant Replacement Therapy [SRT] becomes a lifesaver in such cases. Developing synthetic LS with efficacy in treating ARDS has therefore been a focus of this work. Further, with the rapid development in commercial and biomedical applications of engineered nanoparticles (ENPs), concerns regarding the effect of inhaled nanoparticles on LS function also need to be addressed. In this work, we have used a carbon-based ENP to understand their interactions with model LS. Our studies revealed that the alkyl chain saturation and head group charge of the phospholipids that form the major components of the LS play modulate phospholipid-nanoparticle interactions. We monitored the effect of Engineered Carbon Nanodiamonds [ECN] on five lipid compositions. In a zwitterionic environment, the nanoparticle was line active and favored the phospholipid domain boundaries. However, in an anionic environment, the nanoparticles reduced the packing density between domains. The electrostatic charge interaction was found to be more dominant. We also observed the tug of war between a synthetic surfactant protein (analog of natural surfactant protein, SPB) called MiniB and cholesterol. MiniB increased the line tension of the domains whereas cholesterol reduced the same. MiniB also helped in forming reversible collapse at low surface tension, which in turn saved material loss to the bulk. A lower concentration of both proved to be effective in increasing the surface activity of LS