Interaction of pulmonary surfactant protein A (SP-A) with DPPC/egg-PG bilayers

Abu-Libdeh, Nidal M. (2003) Interaction of pulmonary surfactant protein A (SP-A) with DPPC/egg-PG bilayers. Masters thesis, Memorial University of Newfoundland.

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Abstract

Surfactant protein A (SP-A) is the major protein component of pulmonary surfactant, a material that reduces surface tension at the air-water interface in lungs. This reduction is achieved by forming a phospholipid monolayer. Formation of the monolayer is thought to proceed via an intermediate structure, tubular myelin, in which lipid bilayers are arranged in a lattice of tubes. The minimum requirement for formation of tubular myelin in vitro appears to be the saturated lipid dipalmitoylphosphatidylcholine (DPPC), anionic lipid egg-phosphatidylglycerol (PG), the hydrophobic protein SP-B, and the hydrophilic protein SP-A. SP-A is an octadecamer which is thought to interact with the bilayer surface through its carbohydrates recognition domain (CRD). The interaction of SP-A with DPPC/egg-PG bilayers, in the presence of calcium and with or without SP-B, has been studied using deuterium NMR observations of chain and headgroup deuterated DPPC in protein-lipid mixtures. While the DPPC-d₆₂/egg-PG bilayers liquid crystal-to-gel phase transition was found to proceed continuously in the presence of only SP-A, it was relatively sharp in the presence of SP-A and SP-B. SP-A alone reduces the first spectral moment M₁ for DPPC-d₆₂/egg-PG bilayers in the gel phase. When it is incorporated with SP-B into the DPPC-d₆₂/egg-PG bilayers the first spectral moment, M₁, was found, in the gel phase, to be higher than for the protein-free lipid mixture. These observations suggest that SP-A alone does not remove the effect of egg-PG on the DPPC bilayers and, hence, it has no specific interaction with either lipid component of the mixture. The removal of the effect of egg-PG on DPPC bilayers by SP-A and SP-B together suggests that SP-B may have a preferential interaction with egg-PG or that both proteins interact in a cooperative manner with the egg-PG. Transverse relaxation time (T₂e) studies suggest that SP-A influences slow lipid motions in the liquid crystalline phase. DPPC headgroup studies showed that the presence of SP-A reduces the size of the β quadrupole splittings while the α quadrupole splittings remains unchanged. This was found to be consistent with the increase in area per lipid and, at the same time, with a decrease in the headgroup orientational order resulting from interaction with SP-A. Taken together, these observations are consistent with the expectation that SP-A interacts primarily at the bilayer surface.

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