(634a) Tug of War in Lung Surfactant Components: Effect of Mini B and Cholesterol on Lipid Domain Formation and Collapse

Authors: 
Chakraborty, A., University of Kansas
Dhar, P., University of Kansas
Waring, A. J., University of California Los Angeles
Hui, E., University of Kansas

Lung surfactants [LS] are a complex mixture of lipids and proteins that line up the air-water interface in the alveoli of the lungs. They lower the work of breathing by reducing the surface tension. 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. At present, there is no consensus on the composition of LS used in SRT, particularly the interactions between components making up this mixture. Here, we focus on understanding the interaction between MiniB, a synthetic analog of the natural surfactant protein SPB, and cholesterol, whose purpose and use is highly debated in SRT, in the presence of a simple binary mixture of LS phospholipids, namely, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG). Fluorescence imaging under constant compression, along with analysis of domain size distributions, reveals that MiniB increases line tension between lipid domains, and prefers to stay in fluid POPG regions, making the liquid-ordered domains smaller in size. Small amounts of cholesterol prefer packed domains, stretching them into spirals during the process, lowering their line tension. In both cases, individually, higher concentration yields more prominent consequences in terms of the stated changes. However, mixture containing lower concentration of both proved to be effective in increasing the surface activity of LS. Thus, interaction between the two components may have important effects on the performance of synthetic LS.