Molecular Interactions in Pulmonary Surfactant Films

Pérez‐Gil, Jesús

doi:10.1159/000056765

Cited by 46 publications

(34 citation statements)

References 63 publications

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“…Such interactions are likely to be important in promoting contact between the surfactant monolayer on the alveolar surface and bilayer structures in the subphase surfactant reservoir. Although SDS micelles can be expected to better mimic the in ViVo bilayer environment than HFIP, we opted to use HFIP as well for two reasons: (1) to help in the analysis of the SDS spectra (which have much broader lines than the HFIP spectra) and (2) to give clues about the structural consequences of interactions between the positively charged residues on the peptide with the headgroups of anionic lipids. In both environments, the 10 or 11 C-terminal residues of SP-B CTERM take on a well-defined R-helical structure ( Figure 5).…”

Section: Discussionmentioning

confidence: 99%

“…Surfactant is synthesized and secreted into the alveolar fluid by type II pneumocytes and is composed of approximately 80% phospholipids, 10% neutral lipids, and 10% proteins (1,2). Surfactant-associated water soluble proteins A and D (SP-A and SP-D, respectively) are important for host defense (3,4) but have less impact than the hydrophobic surfactant proteins on the biophysical properties of bilayers and monolayers.…”

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confidence: 99%

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NMR Structures of the C-Terminal Segment of Surfactant Protein B in Detergent Micelles and Hexafluoro-2-propanol

et al. 2004

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Although the membrane-associated surfactant protein B (SP-B) is an essential component of lung surfactant, which is itself essential for life, the molecular basis for its activity is not understood. SP-B's biophysical functions can be partially mimicked by subfragments of the protein, including the C-terminus. We have used NMR to determine the structure of a C-terminal fragment of human SP-B that includes residues 63-78. Structure determination was performed both in the fluorinated alcohol hexafluoro-2-propanol (HFIP) and in sodium dodecyl sulfate (SDS) micelles. In both solvents, residues 68-78 take on an amphipathic helical structure, in agreement with predictions made by comparison to homologous saposin family proteins. In HFIP, the five N-terminal residues of the peptide are largely unstructured, while in SDS micelles, these residues take on a well-defined compact conformation. Differences in helical residue side chain positioning between the two solvents were also found, with better agreement between the structures for the hydrophobic face than the hydrophilic face. A paramagnetic probe was used to investigate the position of the peptide within the SDS micelles and indicated that the peptide is located at the water interface with the hydrophobic face of the helix oriented inward, the hydrophilic face of the helix oriented outward, and the N-terminal residues even farther from the micelle center than those on the hydrophilic face of the R-helix. Interactions of basic residues of SP-B with anionic lipid headgroups are known to have an impact on function, and these studies demonstrate structural ramifications of such interactions via the differences observed between the peptide structures determined in HFIP and SDS.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

NMR Structures of the C-Terminal Segment of Surfactant Protein B in Detergent Micelles and Hexafluoro-2-propanol

et al. 2004

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“…Other pure lipidic preparations incorporated also some proportions of anionic phospholipids [22] and other lipid additives have been assessed as potential agents to improve DPPC dynamics [23], but the idea that an efficient therapeutic surfactant could be designed in the absence of surface active proteins was abandoned soon. In fact, is the action of proteins SP-B and SP-C that greatly facilitates the rapid movement of surface-active lipids between membranes and the interface and helps to re-spread the compressed states of the films during subsequent cycling [8,24]. For this reason, this review will pay special attention to current ideas on the design and production of hydrophobic surfactant protein analogs to develop new artificial surfactants.…”

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confidence: 99%

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Mingarro¹,

Lukovic²,

Vilar³

et al. 2008

CMC

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Pulmonary surfactant is a lipid-protein complex that coats the interior of the alveoli and enables the lungs to function properly. Upon its synthesis, lung surfactant adsorbs at the interface between the air and the hypophase, a capillary aqueous layer covering the alveoli. By lowering and modulating surface tension during breathing, lung surfactant reduces respiratory work of expansion, and stabilises alveoli against collapse during expiration.Pulmonary surfactant deficiency, or dysfunction, contributes to several respiratory pathologies, such as infant respiratory distress syndrome (IRDS) in premature neonates, and acute respiratory distress syndrome (ARDS) in children and adults. The main clinical exogenous surfactants currently in use to treat some of these pathologies are essentially organic extracts obtained from animal lungs. Although very efficient, natural surfactants bear serious defects: i) they could vary in composition from batch to batch; ii) their production involves relatively high costs, and sources are limited; and iii) they carry a potential risk of transmission of animal infectious agents and the possibility of immunological reaction. All these caveats justify the necessity for a highly controlled synthetic material.In the present review the efforts aimed at new surfactant development, including the modification of existing exogenous surfactants by adding molecules that can enhance their activity, and the progress achieved in the production of completely new preparations, are discussed. Pulmonary surfactant function and dysfunctionThe respiratory surface of lungs constitutes the largest area of the human body exposed to the environment. Efficient gas exchange requires a large enough surface to be continuously exposed to air while minimising the barriers for oxygen and carbon dioxide to diffuse between air and the blood compartment [1]. At the same time, a selection of combined defence mechanisms is required to help keep such an essentially exposed area sterile of potential pathogenic microorganisms. Pulmonary surfactant, a lipid-protein complex produced by the alveolar epithelium of lungs, has been optimised to coordinate two main activities through natural evolution. On the one hand, it stabilises the respiratory surface against physical forces, therefore minimising the work required to maintain the large respiratory surface open to air [2][3][4]. On the other hand, pulmonary surfactant contains elements responsible for establishing a primary innate antipathogenic barrier, essential to ensure an intrinsically low pathogen load in the absence of induced defence mechanisms [5]. Extensive research in the last few decades has revealed some of the molecular mechanisms involved in pulmonary surfactant action. However, the manner in which both the biophysical and defence activities are intermingled and coordinately modulated in the alveolar spaces is now only beginning to be envisioned.Pulmonary surfactant is composed of approximately 90% lipids and 8-10% proteins, although only around 5% ...

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“…Pulmonary surfactant is the main secretory product of the alveolar type II pneumocytes and is required to stabilize the lungs in air-breathing animals (1,2). This surfactant material is mainly composed of lipids, mainly phospholipids, and small amounts of specifically associated proteins.…”

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confidence: 99%

“…This surfactant material is mainly composed of lipids, mainly phospholipids, and small amounts of specifically associated proteins. Among the phospholipids significant amounts of dipalmitoylphosphatidylcholine (DPPC) 1 and phosphatidylglycerol are present, both of which are unusual species in most animal membranes. Monounsaturated phosphatidylcholines (PC), phosphatidylinositol, and neutral lipids including cholesterol are also present in pulmonary surfactant in varying proportions.…”

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confidence: 99%

Cholesterol Rules

Serna¹,

Pérez‐Gil²,

Simonsen³

et al. 2004

Journal of Biological Chemistry

263

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Pulmonary surfactant, the lipid-protein material that stabilizes the respiratory surface of the lungs, contains approximately equimolar amounts of saturated and unsaturated phospholipid species and significant proportions of cholesterol. Such lipid composition suggests that the membranes taking part in the surfactant structures could be organized heterogeneously in the form of inplane domains, originating from particular distributions of specific proteins and lipids. Here we report novel results concerning the lateral organization of bilayer membranes made of native pulmonary surfactant where the coexistence of two distinct micrometer sized fluid phases (fluid ordered and fluid disordered-like phases) is observed at physiological temperatures by using fluorescence microscopy and atomic force microscopy. Additional experiments using fluorescent-labeled proteins SP-B and SP-C show that at physiological temperatures these hydrophobic proteins are located exclusively in the fluid disordered-like phase. Most interestingly, the microscopic coexistence of fluid phases is maintained up to 37.5°C, where most fluid ordered phases melt. This observation suggests that the particular composition of this material is naturally designed to be at the "edge" of a lateral structure transition under physiological conditions, likely providing particular structural and dynamic properties for its mechanical function. The observed lateral structure in native pulmonary surfactant membranes is dramatically affected by the extraction of cholesterol, an effect not observed upon extraction of the surfactant proteins. Furthermore, the spreading properties of the native surfactant material at the air-liquid interface were also greatly affected by cholesterol extraction, suggesting a connection between the observed lateral structure and a physiologically relevant function of the material. We suggest that the particular lipid composition of surfactant could be finely tuned to provide, under physiological conditions, a structural scaffold for surfactant proteins to act at appropriate local densities and lipid composition.

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Molecular Interactions in Pulmonary Surfactant Films

Cited by 46 publications

References 63 publications

NMR Structures of the C-Terminal Segment of Surfactant Protein B in Detergent Micelles and Hexafluoro-2-propanol

NMR Structures of the C-Terminal Segment of Surfactant Protein B in Detergent Micelles and Hexafluoro-2-propanol

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Cholesterol Rules

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