The Effects of Free Radical-induced Epoxidation and Peroxidation of Unsaturated Phospholipids on the Self-assembly of Functional Surfactant Film
Abstract
The pulmonary surfactant is a protein-lipid mixture that covers the air-water interface. It lowers the alveolar surface tension to near zero values. Surfactant dysfunction has been reported in acute lung injury, acute respiratory distress syndrome, and cystic fibrosis, among other inflammatory lung diseases. Surfactant achieves low surface tension by forming a tightly packed uniform film at the air-water interface and thus, eliminates the electrostatic forces between liquid molecules. As the film pressure (π) increase, surfactant explores a third dimension or multilayers. Monolayer-Multilayer interactions provide additional stability to resist the varying high film pressure at the air-water interface, therefore, preventing premature buckling of the interfacial film.
The surfactant may become impaired during pulmonary inflammation, where free radicals degrade its components, whether by introducing epoxides and hydroperoxides to the tightly packed hydrocarbon tails of surfactant phospholipids or by fatty acyl tail fragmentation. In this thesis, we show that oxidation mediated surfactant inhibition is cholesterol dependent. We study surfactant film thermodynamic changes as a result of oxidation and cholesterol. Additionally, we show the structure-function relationship and the underlying importance of monolayer-multilayer anchoring. Moreover, we show that multilayer distribution and arrangements due to oxidized cholesterol species do not alter surfactant film function. Further, we modeled the surfactant film via mechanical finite element analysis software (ANSYS) to examine the role of multilayers. We predict that the mechanism of surfactant dysfunction demonstrated in vitro is relevant to disease state.
Description
Keywords
Biophysics--Medical, Chemistry--Organic
Citation
Al-Saiedy, M. (2016). The Effects of Free Radical-induced Epoxidation and Peroxidation of Unsaturated Phospholipids on the Self-assembly of Functional Surfactant Film (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28103