TitleVibrational spectroscopic and related studies of lipid/protein interaction in lung surfactant models
NameMao, Guangru (author), Mendelsohn, Richard (chair), He, Huixin (internal member), Lalancette, Roger (internal member), Walters, Russel M (outside member), Rutgers University, Graduate School - Newark,
DescriptionLung surfactant, a lipid/protein complex located at the air/alveolar lining of the mammalian lung, facilitates the work of breathing and prevents alveolar collapse. Lung surfactant associated proteins SP-A and SP-D are also involved in pulmonary innate immune response. The deficiency or dysfunction of lung surfactant may lead to pathological conditions of lungs. The "squeeze out" hypothesis was proposed in 1960s to explain the mechanism of the surface tension lowering functions of lung surfactant. It suggests that non-DPPC components are squeezed out during expiration from the monolayer and form a multilayer structure attached underneath the monolayer at high compressions. This multilayer structure serves as a surfactant reservoir to supply surfactant for the following surface expansion. Multilamellar structures have been observed in alveolar surface film and with lung surfactant models; however, its composition is not known thoroughly. In this thesis, substrate-supported films were transferred from air/water interface by a novel technique termed "COVASP", which transfers films under continuous surface compression. Model lung surfactant systems containing DPPC, DPPG, SP-C and cholesterol were used in this study. The COVASP films with a broad surface pressure coverage were characterized by IR imaging. The relative composition of multilayers was probed by the IR absorbance of characteristic vibrational modes for each component. The results showed that both phospholipids and SP-C were present in multilayers, but DPPC was concentrated to a lesser extent compared to DPPG and SP-C. The application of COVASP-IR imaging was further extended to evaluate the synthetic biomimetics of lung surfactant SP-C for potential therapeutic use. A class of N-substituted polyglycine molecules with helical structures has been synthesized as SP-C mimics by our collaborators. The ability of these peptoids to form multilayers was studied by COVASP and AFM and was compared to native SP-C. It is found that palmitoylated peptoid was able to form multilayers with lung surfactant model used, but only at a higher peptoid concentration. In addition, the extent of multilayer formation was also lower when compared to SP-C. As a component of pulmonary innate immune system, SP-A directly binds to a series of bacteria and microbes. LPS, constituents of bacterial outer membrane, are ligands of SP-A. The mode of interaction between SP-A and LPS was studied by IRRAS. It is speculated that SP-A interacted with LPS acyl chains in a Ca2+ dependent manner. Truncated SP-A was also studied and was compared to its hyperpermeabilizing mutant D215A/PL SP-A. D215A/PL SP-A was more stable at the air/water interface, which may contribute to its hyperpermeability.
NoteIncludes bibliographical references
Noteby Guangru Mao
CollectionGraduate School - Newark Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.