Tubular myelin is a form of pulmonary surfactant which has a unique lamellar structure, possibly resulting from a fusion of phospholipid bilayers at fairly regular, long-range intervals. This structure markedly affects the surface properties of surfactant, and materials of similar composition, but different morphology, function less satisfactorily as alveolar surfactants. Previous work has shown that an apolipoprotein specifically found in pulmonary surfactant, and Ca2+ ions, are required for this structure. The work in this proposal will investigate the physical properties of recombinant complexes formed between certain phospholipids and this apolipoprotein, with the overall goal of using this relatively simple system to obtain information that can be applied to the analysis of the more complicated natural surfactant. The experiments are developed around 4 broad objectives: (1) to determine if the apolipoprotein, upon binding lamellar lipids, will induce a lateral phase separation; (2) to characterize the physical state of the phospholipid in the immediate environment of the bound apolipoprotein; (3) to describe the secondary structure of the apolipoprotein in solutions, and to determine if it changes upon interaction with the phospholipid; and (4) to determine if the surface properties of the recombinants can be correlated with the observed differences in lamellar organization. These physical properties will be analyzed by the measurement of surface tension, steady-state fluorescence anisotropy, differential scanning calorimetry, and circular dichroism.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL019676-11
Application #
3335891
Study Section
(SSS)
Project Start
1977-01-01
Project End
1989-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
11
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
Overall Medical
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
King, R J; Simon, D; Horowitz, P M (1989) Aspects of secondary and quaternary structure of surfactant protein A from canine lung. Biochim Biophys Acta 1001:294-301
King, R J; Phillips, M C; Horowitz, P M et al. (1986) Interaction between the 35 kDa apolipoprotein of pulmonary surfactant and saturated phosphatidylcholines. Effects of temperature. Biochim Biophys Acta 879:1-13