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1
Creuwels, Lambert A. J. M., Lambert M. G. van Golde, and Henk P. Haagsman. "Surfactant protein B: effects on lipid domain formation and intermembrane lipid flow." Biochimica et Biophysica Acta (BBA) - Biomembranes 1285, no. 1 (November 1996): 1–8. http://dx.doi.org/10.1016/s0005-2736(96)00131-9.
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Qanbar, R., S. Cheng, F. Possmayer, and S. Schurch. "Role of the palmitoylation of surfactant-associated protein C in surfactant film formation and stability." American Journal of Physiology-Lung Cellular and Molecular Physiology 271, no. 4 (October 1, 1996): L572—L580. http://dx.doi.org/10.1152/ajplung.1996.271.4.l572.
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The effect of palmitoylation of pulmonary surfactant-associated protein C (SP-C) on the surface activity of phospholipid mixtures of dipalmitoylphosphatidylcholine and phosphatidylglycerol was studied. Phospholipids reconstituted with palmitoylated or depalmitoylated bovine SP-C were examined at neutral and acidic pH using a captive bubble surfactometer. At low pH, effective lipid adsorption and near zero surface tensions upon compression were obtained even with protein-free samples. At physiological pH, only SP-C-containing samples achieved such properties. Lipid adsorption was decreased by prior SP-C depalmitoylation. Bubbles with palmitoylated SP-C were more mechanically stable and required less compression to reach low surface tensions. Subphase depletion experiments showed that dynamically cycled surface layers containing palmitoylated SP-C maintained their surface activity after subphase lipid depletion. In contrast, surface activity was rapidly lost where depalmitoylated SP-C or SP-B was included. Our results indicate that although SP-C palmitoylation has little effect on its ability to enhance lipid adsorption and surface tension reduction, it greatly enhances lipid respreading and film stability and is therefore important for surfactant function.
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Palaniyar, Nades, Ross A. Ridsdale, Stephen A. Hearn, Fred Possmayer, and George Harauz. "Formation of membrane lattice structures and their specific interactions with surfactant protein A." American Journal of Physiology-Lung Cellular and Molecular Physiology 276, no. 4 (April 1, 1999): L642—L649. http://dx.doi.org/10.1152/ajplung.1999.276.4.l642.
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Biological membranes exist in many forms, one of which is known as tubular myelin (TM). This pulmonary surfactant membranous structure contains elongated tubes that form square lattices. To understand the interaction of surfactant protein (SP) A and various lipids commonly found in TM, we undertook a series of transmission-electron-microscopic studies using purified SP-A and lipid vesicles made in vitro and also native surfactant from bovine lung. Specimens from in vitro experiments were negatively stained with 2% uranyl acetate, whereas fixed native surfactant was delipidated, embedded, and sectioned. We found that dipalmitoylphosphatidylcholine-egg phosphatidylcholine (1:1 wt/wt) bilayers formed corrugations, folds, and predominantly 47-nm-square latticelike structures. SP-A specifically interacted with these lipid bilayers and folds. We visualized other proteolipid structures that could act as intermediates for reorganizing lipids and SP-As. Such a reorganization could lead to the localization of SP-A in the lattice corners and could explain, in part, the formation of TM-like structures in vivo.
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Johansson, J. "Membrane properties and amyloid fibril formation of lung surfactant protein C." Biochemical Society Transactions 29, no. 4 (August 1, 2001): 601–6. http://dx.doi.org/10.1042/bst0290601.
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Pulmonary surfactant is essential for respiration and lung host defence and is composed of 80–90% lipids, mainly dipalmitoylphosphatidylcholine (DPPC). Surfactant protein C (SP-C) constitutes 1–2 % of the surfactant mass, and is one of the most hydrophobic peptides yet isolated. SP-C residues 9–34 form an α-helix with a central poly-valine segment, which perfectly matches the thickness of a fluid DPPC bilayer. The palmitoyl groups linked to Cys-5 and Cys-6 of SP-C increase the capacity of the peptide to promote lipid adsorption at an air/liquid interface, and augment the mechanical stability of SP-C/lipid mixtures. SP-C undergoes α-helix → β-sheet transition and forms amyloid fibrils. NMR and MS studies show that the poly-valine helix is kinetically stabilized, and that once it unfolds, formation of β-sheet aggregates is significantly faster than refolding. α-Helix unfolding is accelerated after removal of the palmitoyl groups. Secondary structure prediction of SP-C yields β-strand conformation of the poly-valine part. A database search revealed similar discordance between experimentally determined helices and predicted β-strands for other amyloid-forming proteins, including the prion protein associated with spongiform encephalopathies, and the amyloid-β (Aβ) peptide associated with Alzheimer's disease. For Aβ and SP-C, removal of the helix/strand discordance by residue replacements abrogates fibril formation in vitro.
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Krol, Silke, Michaela Ross, Manfred Sieber, Stephanie Künneke, Hans-Joachim Galla, and Andreas Janshoff. "Formation of Three-Dimensional Protein-Lipid Aggregates in Monolayer Films Induced by Surfactant Protein B." Biophysical Journal 79, no. 2 (August 2000): 904–18. http://dx.doi.org/10.1016/s0006-3495(00)76346-6.
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Pérez-Gil, Jesus, Jacqueline Tucker, Gary Simatos, and Kevin M. W. Keough. "Interfacial adsorption of simple lipid mixtures combined with hydrophobic surfactant protein from pig lung." Biochemistry and Cell Biology 70, no. 5 (May 1, 1992): 332–38. http://dx.doi.org/10.1139/o92-051.
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Hydrophobic pulmonary surfactant protein enriched in SP-C has been mixed in amounts up to 10% by weight with various phospholipids. The lipids used were dipalmitoyl phosphatidylcholine (DPPC), or DPPC plus unsaturated phosphatidylglycerol (PG), or phosphatidylinositol (PI) in molar ratios of 9:1 and 7:3. The protein enhanced the rate and extent of adsorption of each lipid preparation into the air–water interface, and its respreading after compression on a surface balance. Maximum surface pressures attained on compression of monolayers of mixtures of lipids were slightly higher in the presence of protein. The effects on rate and extent of adsorption were proportional to the amount of protein present. Mixtures containing 30 mol% PG or PI adsorbed more readily into the interface than those containing 10% acidic lipid or DPPC alone. Mixtures containing 30% PI were slightly more rapidly adsorbed than those containing 30% PG. The results suggest that mixtures of DPPC with either acidic lipid in the presence of surfactant protein could be effective in artificial surfactants.Key words: pulmonary surfactant, monolayer formation, adsorption, synthetic surfactant, proteolipids.
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Bates, Sandra R., Jian-Qin Tao, Kathleen Notarfrancesco, Kristine DeBolt, Henry Shuman, and Aron B. Fisher. "Effect of surfactant protein A on granular pneumocyte surfactant secretion in vitro." American Journal of Physiology-Lung Cellular and Molecular Physiology 285, no. 5 (November 2003): L1055—L1065. http://dx.doi.org/10.1152/ajplung.00271.2002.
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Surfactant secretion by lung type II cells occurs when lamellar bodies (LBs) fuse with the plasma membrane and surfactant is released into the alveolar lumen. Surfactant protein A (SP-A) blocks secretagogue-stimulated phospholipid (PL) release, even in the presence of surfactant-like lipid. The mechanism of action is not clear. We have shown previously that an antibody to LB membranes (MAb 3C9) can be used to measure LB membrane trafficking. Although the ATP-stimulated secretion of PL was blocked by SP-A, the cell association of iodinated MAb 3C9 was not altered, indicating no effect on LB movement. FM1-43 is a hydrophobic dye used to monitor the formation of fusion pores. After secretagogue exposure, the threefold enhancement of the number of FM1-43 fluorescent LBs (per 100 cells) was not altered by the presence of SP-A. Finally, there was no evidence of a large PL pool retained on the cell surface through interaction with SP-A. Thus SP-A exposure does not affect these stages in the surfactant secretory pathway of type II cells.
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Palaniyar, Nades, Ross A. Ridsdale, Stephen A. Hearn, Yew Meng Heng, F. Peter Ottensmeyer, Fred Possmayer, and George Harauz. "Filaments of surfactant protein A specifically interact with corrugated surfaces of phospholipid membranes." American Journal of Physiology-Lung Cellular and Molecular Physiology 276, no. 4 (April 1, 1999): L631—L641. http://dx.doi.org/10.1152/ajplung.1999.276.4.l631.
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Pulmonary surfactant, a mixture of lipids and surfactant proteins (SPs), plays an important role in respiration and gas exchange. SP-A, the major SP, exists as an octadecamer that can self-associate to form elongated protein filaments in vitro. We have studied here the association of purified bovine SP-A with lipid vesicle bilayers in vitro with negative staining with uranyl acetate and transmission electron microscopy. Native bovine surfactant was also examined by transmission electron microscopy of thinly sectioned embedded material. Lipid vesicles made from dipalmitoylphosphatidylcholine and egg phosphatidylcholine (1:1 wt/wt) generally showed a smooth surface morphology, but some large vesicles showed a corrugated one. On the smooth-surfaced vesicles, SP-As primarily interacted in the form of separate octadecamers or as multidirectional protein networks. On the surfaces of the striated vesicles, SP-As primarily formed regularly spaced unidirectional filaments. The mean spacing between adjacent striations and between adjacent filaments was 49 nm. The striated surfaces were not essential for the formation of filaments but appeared to stabilize them. In native surfactant preparations, SP-A was detected in the dense layers. This latter arrangement of the lipid bilayer-associated SP-As supported the potential relevance of the in vitro structures to the in vivo situation.
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Frey, Shelli L., Luka Pocivavsek, Alan J. Waring, Frans J. Walther, Jose M. Hernandez-Juviel, Piotr Ruchala, and Ka Yee C. Lee. "Functional importance of the NH2-terminal insertion sequence of lung surfactant protein B." American Journal of Physiology-Lung Cellular and Molecular Physiology 298, no. 3 (March 2010): L335—L347. http://dx.doi.org/10.1152/ajplung.00190.2009.
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Lung surfactant protein B (SP-B) is required for proper surface activity of pulmonary surfactant. In model lung surfactant lipid systems composed of saturated and unsaturated lipids, the unsaturated lipids are removed from the film at high compression. It is thought that SP-B helps anchor these lipids closely to the monolayer in three-dimensional cylindrical structures termed “nanosilos” seen by atomic force microscopy imaging of deposited monolayers at high surface pressures. Here we explore the role of the SP-B NH2 terminus in the formation and stability of these cylindrical structures, specifically the distribution of lipid stack height, width, and density with four SP-B truncation peptides: SP-B 1–25, SP-B 9–25, SP-B 11–25, and SP-B 1–25Nflex (prolines 2 and 4 substituted with alanine). The first nine amino acids, termed the insertion sequence and the interface seeking tryptophan residue 9, are shown to stabilize the formation of nanosilos while an increase in the insertion sequence flexibility (SP-B 1–25Nflex) may improve peptide functionality. This provides a functional understanding of the insertion sequence beyond anchoring the protein to the two-dimensional membrane lining the lung, as it also stabilizes formation of nanosilos, creating reversible repositories for fluid lipids at high compression. In lavaged, surfactant-deficient rats, instillation of a mixture of SP-B 1–25 (as a monomer or dimer) and synthetic lung lavage lipids quickly improved oxygenation and dynamic compliance, whereas SP-B 11–25 surfactants showed oxygenation and dynamic compliance values similar to that of lipids alone, demonstrating a positive correlation between formation of stable, but reversible, nanosilos and in vivo efficacy.
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Miles, P. R., L. Bowman, K. M. K. Rao, J. E. Baatz, and L. Huffman. "Pulmonary surfactant inhibits LPS-induced nitric oxide production by alveolar macrophages." American Journal of Physiology-Lung Cellular and Molecular Physiology 276, no. 1 (January 1, 1999): L186—L196. http://dx.doi.org/10.1152/ajplung.1999.276.1.l186.
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The objectives of this investigation were 1) to report that pulmonary surfactant inhibits lipopolysaccharide (LPS)-induced nitric oxide (⋅ NO) production by rat alveolar macrophages, 2) to study possible mechanisms for this effect, and 3) to determine which surfactant component(s) is responsible. ⋅ NO produced by the cells in response to LPS is due to an inducible ⋅ NO synthase (iNOS). Surfactant inhibits LPS-induced ⋅ NO formation in a concentration-dependent manner; ⋅ NO production is inhibited by ∼50 and ∼75% at surfactant levels of 100 and 200 μg phospholipid/ml, respectively. The inhibition is not due to surfactant interference with the interaction of LPS with the cells or to disruption of the formation of iNOS mRNA. Also, surfactant does not seem to reduce ⋅ NO formation by directly affecting iNOS activity or by acting as an antioxidant or radical scavenger. However, in the presence of surfactant, there is an ∼80% reduction in the amount of LPS-induced iNOS protein in the cells. LPS-induced ⋅ NO production is inhibited by Survanta, a surfactant preparation used in replacement therapy, as well as by natural surfactant. ⋅ NO formation is not affected by the major lipid components of surfactant or by two surfactant-associated proteins, surfactant protein (SP) A or SP-C. However, the hydrophobic SP-B inhibits ⋅ NO formation in a concentration-dependent manner; ⋅ NO production is inhibited by ∼50 and ∼90% at SP-B levels of 1–2 and 10 μg/ml, respectively. These results show that lung surfactant inhibits LPS-induced ⋅ NO production by alveolar macrophages, that the effect is due to a reduction in iNOS protein levels, and that the surfactant component responsible for the reduction is SP-B.
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Rodriguez-Capote, Karina, Kaushik Nag, Samuel Schürch, and Fred Possmayer. "Surfactant protein interactions with neutral and acidic phospholipid films." American Journal of Physiology-Lung Cellular and Molecular Physiology 281, no. 1 (July 1, 2001): L231—L242. http://dx.doi.org/10.1152/ajplung.2001.281.1.l231.
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The captive bubble tensiometer was employed to study interactions of phospholipid (PL) mixtures of dipalmitoylphosphatidylcholine (DPPC) and 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine (POPC) or 1-palmitoyl-2-oleoyl- sn-glycero-3-[phospho- rac-(1-glycerol)] (POPG) at 50 μg/ml with physiological levels of the surfactant protein (SP) A SP-B, and SP-C alone and in combination at 37°C. All surfactant proteins enhanced lipid adsorption to equilibrium surface tension (γ), with SP-C being most effective. Kinetics were consistent with the presence of two adsorption phases. Under the conditions employed, SP-A did not affect the rate of film formation in the presence of SP-B or SP-C. Little difference in γmin was observed between the acidic POPG and the neutral POPC systems with SP-B or SP-C with and without SP-A. However, γmax was lower with the acidic POPG system during dynamic, but not during quasi-static, cycling. Considerably lower compression ratios were required to generate low γminvalues with SP-B than SP-C. DPPC-POPG-SP-B was superior to the neutral POPC-SP-B system. Although SP-A had little effect on film formation with SP-B, surface activity during compression was enhanced with both PL systems. In the presence of SP-C, lower compression ratios were required with the acidic system, and with this mixture, SP-A addition adversely affected surface activity. The results suggest specific interactions between SP-B and phosphatidylglycerol, and between SP-B and SP-A. These observations are consistent with the presence of a surface-associated surfactant reservoir which is involved in generating low γ during film compression and lipid respreading during film expansion.
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Waring, Alan J., Julian P. Whitelegge, Shantanu K. Sharma, Larry M. Gordon, and Frans J. Walther. "Emulation of the structure of the Saposin protein fold by a lung surfactant peptide construct of surfactant Protein B." PLOS ONE 17, no. 11 (November 3, 2022): e0276787. http://dx.doi.org/10.1371/journal.pone.0276787.
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The three-dimensional structure of the synthetic lung Surfactant Protein B Peptide Super Mini-B was determined using an integrative experimental approach, including mass spectrometry and isotope enhanced Fourier-transform infrared (FTIR) spectroscopy. Mass spectral analysis of the peptide, oxidized by solvent assisted region-specific disulfide formation, confirmed that the correct folding and disulfide pairing could be facilitated using two different oxidative structure-promoting solvent systems. Residue specific analysis by isotope enhanced FTIR indicated that the N-terminal and C-terminal domains have well defined α-helical amino acid sequences. Using these experimentally derived measures of distance constraints and disulfide connectivity, the ensemble was further refined with molecular dynamics to provide a medium resolution, residue-specific structure for the peptide construct in a simulated synthetic lung surfactant lipid multilayer environment. The disulfide connectivity combined with the α-helical elements stabilize the peptide conformationally to form a helical hairpin structure that resembles critical elements of the Saposin protein fold of the predicted full-length Surfactant Protein B structure.
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Tian, Yong, Ruobing Zhou, Jerold E. Rehg, and Suzanne Jackowski. "Role of Phosphocholine Cytidylyltransferase α in Lung Development." Molecular and Cellular Biology 27, no. 3 (November 27, 2006): 975–82. http://dx.doi.org/10.1128/mcb.01512-06.
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ABSTRACT Lung development depends upon the differentiation and expansion of a variety of specialized epithelial cell types, including distal type I and type II pneumocytes in the late term. Previous studies have shown a strict dependence on the choline cytidylyltransferase α isoform (CCTα) to mediate membrane phospholipid formation in cultured cells and during preimplantation embryogenesis. CCTα expression is highest in lung, and there has long been speculation about its precise role, due to the dual requirement for phospholipid in proliferating cell membranes and for lung surfactant production from alveolar type II cells. We investigated the function of CCTα in lung development, using an inducible, epithelial cell-specific CCTα knockout mouse line. Deletion of CCTα beginning at embryonic day 7.5 did not restrict lung development but resulted in severe respiratory failure at birth. Alveolar lavage and lung lipid analyses showed significant decreases in the major surfactant phospholipid, dipalmitoyl-phosphatidylcholine. The fatty acids destined for the surfactant phospholipid were redirected to an expanded triglyceride pool. Transcripts encoding type II cell-specific markers were expressed in the knockout mice, indicating the expected progression of differentiation in lung epithelia. However, surfactant protein levels were reduced, with the exception of that for surfactant protein B, which was elevated. Ultrastructural analysis of the type II cells showed Golgi complex abnormalities and aberrant lamellar bodies, which deliver surfactant lipid and protein to the alveolar lumen. Thus, CCTα was not required for the proliferation or differentiation of lung epithelia but was essential for the secretory component of phospholipid synthesis and critical for the proper formation of lamellar bodies and surfactant protein homeostasis.
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Giudice, Rita Del, Nicolò Paracini, Tomas Laursen, Clement Blanchet, Felix Roosen-Runge, and Marité Cárdenas. "Expanding the Toolbox for Bicelle-Forming Surfactant–Lipid Mixtures." Molecules 27, no. 21 (November 7, 2022): 7628. http://dx.doi.org/10.3390/molecules27217628.
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Bicelles are disk-shaped models of cellular membranes used to study lipid–protein interactions, as well as for structural and functional studies on transmembrane proteins. One challenge for the incorporation of transmembrane proteins in bicelles is the limited range of detergent and lipid combinations available for the successful reconstitution of proteins in model membranes. This is important, as the function and stability of transmembrane proteins are very closely linked to the detergents used for their purification and to the lipids that the proteins are embedded in. Here, we expand the toolkit of lipid and detergent combinations that allow the formation of stable bicelles. We use a combination of dynamic light scattering, small-angle X-ray scattering and cryogenic electron microscopy to perform a systematic sample characterization, thus providing a set of conditions under which bicelles can be successfully formed.
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Tazhibayeva, Sagdat, Kuanyshbek Musabekov, Zhenis Kusainova, Ardak Sapieva, and Nurlan Musabekov. "Complex Formation of Polyacrylic Acid with Surfactants of Different Hydrophobicity." Applied Mechanics and Materials 752-753 (April 2015): 212–16. http://dx.doi.org/10.4028/www.scientific.net/amm.752-753.212.
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Complex formation processes of polyelectrolytes with surfactant ions are close model to protein - lipid interactions in living organisms. Furthermore, polymer – surfactant complexes are widely used as stabilizers of industrial dispersions and structurants of soil. When using the polymer-surfactant complexes the hydrophilic-lipophilic balance has the great importance. The interaction of polyacrylic acid with alkylammonium salts of different hydrophobicity: cetyltrimethylammonium bromide, dilaurildimethylammonium bromide and dioctadecyldimethylammonium chloride was studied by potentiometry, spectrophotometry, viscometry and electrophoresis methods. It was established that the complex formation of polyacrylic acid with cationic surfactants is carried out due to the electrostatic interaction between carboxyl groups of the polymer and cations of surfactants, which stabilized by hydrophobic interactions between their non-polar parts. The phenomenon of hysteresis in the change of the reduced viscosity of system surfactant /polyacrylic acid with temperature variation in the range of 20-60 °C was found. The possibility of using the complex formation process for water purification from CTAB has been shown. The degree of purification is 99.6-99.8%.
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Wright, J. R., and D. C. Youmans. "Degradation of surfactant lipids and surfactant protein A by alveolar macrophages in vitro." American Journal of Physiology-Lung Cellular and Molecular Physiology 268, no. 5 (May 1, 1995): L772—L780. http://dx.doi.org/10.1152/ajplung.1995.268.5.l772.
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Pulmonary surfactant is synthesized and secreted into the airspaces by the alveolar type II cell. After it is secreted, surfactant undergoes a series of poorly understood transformations resulting in formation of a surface tension-reducing surface at the air-liquid interface. The by-products of the surface film and/or other products of surfactant metabolism are eventually cleared from the alveolar space. Both the alveolar type II cell and the macrophage are thought to be involved in surfactant clearance and have been shown to internalize surfactant lipid in vitro. The goal of the current investigation was to characterize further and to quantitate the role of the macrophage in surfactant clearance by investigating the uptake and metabolism of surfactant lipids and surfactant protein A (SP-A) by macrophages in vitro. SP-A enhanced the uptake of lipids by macrophages in a time-, temperature-, and concentration-dependent manner. In contrast, neither of the collagen-like proteins SP-D or C1q enhanced the uptake. Phosphatidylcholine was rapidly degraded by macrophages and the degradation occurred both in the presence and absence of SP-A. In addition, macrophages degrade SP-A by a process that is time- and temperature-dependent. These results and calculations of uptake and degradation rates suggest that macrophages may contribute significantly to the process of surfactant clearance.
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Lipp, Michael M. "Monolayer Morphology and Collapse Induced by Lung Surfactant Protein: Observation Via Fluorescence and Atomic Force Microscopy." Proceedings, annual meeting, Electron Microscopy Society of America 54 (August 11, 1996): 322–23. http://dx.doi.org/10.1017/s0424820100164076.
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Understanding the role of lung surfactant specific proteins in lipid monolayers is essential for improved treatments for Respiratory Distress Syndrome, which is a leading cause of death in premature infants. Fluorescence (FM) and Atomic Force (AFM) microscopies reveal that the amino-terminal peptide of lung surfactant protein SP-B alters the behavior of palmitic acid (PA) monolayers, enhancing their in vivo performance. The combination of these techniques provides an excellent correlation between the protein-lipid interactions on the molecular level with the macroscopic properties of the monolayer.SP-B protein incorporates into monolayers of PA, an important component of natural and synthetic lung surfactants monolayers. The effect of the protein on the monolayer is evidenced in the isotherm data shown in Fig 1, in which the area per PA molecule, compressibility, and surface pressure at collapse all increase as a function of increasing protein concentration. The protein accomplishes this by inhibiting the formation of ordered phases of PA. This is seen via FM as a transition from a homogeneous, dark ordered phase without protein (Fig 2a) to a network of a disordered, bright phase (the fluorescent lipid probes used in this study prefer to partition into disordered phases, making them appear as bright regions in FM images) that separates ordered phase domains at coexistence (Fig. 2b). The network is stabilized by the low line tension between the bright phase and other lipid phases as confirmed by the formation of extended linear domains of bright phase in a dark background, or “stripe” phases (Fig. 3a) under certain subphase conditions. Similar stripe phases also occur in single component fluorescein-labeled SP-B monolayers (Fig 3b), implying that the protein is responsible for the reduction in line tension. The formation of the fluid phase network is responsible for the increased collapse resistance of these mixed monolayers. The mechanism of collapse shifts from a heterogeneous process of nucleation and growth of large rigid crystalline collapse phases (Fig. 4a) to a more homogeneous process with nucleation and growth of smaller domains distributed uniformly across the film (Fig. 4b). This is due to the protein-induced network breaking up and isolating the domains of ordered phase, effectively lowering the probability of finding a heterogeneous nucleation site within each domain (analagous to the classic experiments of Turnbull on supercooled microemulsions of metallic liquids). The partitioning of the protein into the bright phase network was confirmed through the use of a dual-probe system. Fluorescein-labeled SP-B was added to a PA monolayer incorporating a fluorescent lipid analogue that emits at a higher wavelength. Upon imaging the same region of a monolayer at the different wavelengths (Fig. 5a and 5b), the protein is seen to be located in the bright phase network regions as expected.
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Diemel, Robert V., Margot M. E. Snel, Alan J. Waring, Frans J. Walther, Lambert M. G. van Golde, Günther Putz, Henk P. Haagsman, and Joseph J. Batenburg. "Multilayer Formation upon Compression of Surfactant Monolayers Depends on Protein Concentration as Well as Lipid Composition." Journal of Biological Chemistry 277, no. 24 (March 28, 2002): 21179–88. http://dx.doi.org/10.1074/jbc.m111758200.
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Robichaud, Nicholas A. S., Mohammad Hassan Khatami, Ivan Saika-Voivod, and Valerie Booth. "All-Atom Molecular Dynamics Simulations of Dimeric Lung Surfactant Protein B in Lipid Multilayers." International Journal of Molecular Sciences 20, no. 16 (August 8, 2019): 3863. http://dx.doi.org/10.3390/ijms20163863.
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Although lung surfactant protein B (SP-B) is an essential protein that plays a crucial role in breathing, the details of its structure and mechanism are not well understood. SP-B forms covalent homodimers, and in this work we use all-atom molecular dynamics simulations to study dimeric SP-B’s structure and its behavior in promoting lipid structural transitions. Four initial system configurations were constructed based on current knowledge of SP-B’s structure and mechanism, and the protein maintained a helicity consistent with experiment in all systems. Several SP-B-induced lipid reorganization behaviors were observed, and regions of the protein particularly important for these activities included SP-B’s “central loop” and “hinge” regions. SP-B dimers with one subunit initially positioned in each of two adjacent bilayers appeared to promote close contact between two bilayers. When both subunits were initially positioned in the same bilayer, SP-B induced the formation of a defect in the bilayer, with water penetrating into the centre of the bilayer. Similarly, dimeric SP-B showed a propensity to interact with preformed interpores in the bilayer. SP-B dimers also promoted bilayer thinning and creasing. This work fleshes out the atomistic details of the dimeric SP-B structures and SP-B/lipid interactions that underlie SP-B’s essential functions.
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Poulain, F. R., L. Allen, M. C. Williams, R. L. Hamilton, and S. Hawgood. "Effects of surfactant apolipoproteins on liposome structure: implications for tubular myelin formation." American Journal of Physiology-Lung Cellular and Molecular Physiology 262, no. 6 (June 1, 1992): L730—L739. http://dx.doi.org/10.1152/ajplung.1992.262.6.l730.
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Tubular myelin is one of several forms of lung surfactant and may play an important role in its surface activity. To determine possible mechanisms of tubular myelin formation, we studied the effects of purified surfactant proteins (SP-A, SP-B, and SP-C) on large unilamellar dipalmitoylphosphatidylcholine-egg phosphatidylglycerol (7/3; wt/wt) liposomes. We studied different types of membrane interaction induced by the apolipoproteins and correlated these with the observed changes in ultrastructure. Aggregation was assessed by measurement of light absorbance, lysis, and fusion by measurement of the fluorescence emitted by water-soluble and lipid-soluble probes, respectively. Mixtures of the apolipoproteins and liposomes were examined in ultrastructural studies by negative staining and by thin sectioning. We found that each protein had a pronounced and distinct effect on liposome structure. SP-A caused aggregation, whereas SP-B and SP-C also caused extensive leakage of liposome contents (lysis) and some degree of lipid mixing (fusion). The disruptive effects of SP-B and to a lesser extent those of SP-C were correlated by negative staining with the appearance of bilayer disks, which tended to aggregate into large sheets. There was a marked synergy between SP-A and SP-B in the process of membrane fusion in the presence of calcium, which correlated with an early (10 min) and extensive rearrangement of the structures seen by electron microscopy followed by a delayed (24 h) appearance of small amounts of tubular myelin.
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Fujiwara, Shougo, Kan Shoji, Chiho Watanabe, Ryuji Kawano, and Miho Yanagisawa. "Microfluidic Formation of Honeycomb-Patterned Droplets Bounded by Interface Bilayers via Bimodal Molecular Adsorption." Micromachines 11, no. 7 (July 20, 2020): 701. http://dx.doi.org/10.3390/mi11070701.
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Assembled water-in-oil droplets bounded by lipid bilayers are used in synthetic biology as minimal models of cell tissue. Microfluidic devices successfully generate monodispersed droplets and assemble them via droplet interface bilayesr (DIB) formation. However, a honeycomb pattern of DIB-bounded droplets, similar to epithelial tissues, remains unrealized because the rapid DIB formation between the droplets hinders their ability to form the honeycomb pattern. In this paper, we demonstrate the microfluidic formation of a honeycomb pattern of DIB-bounded droplets using two surfactants with different adsorption rates on the droplet surface. A non-DIB forming surfactant (sorbitan monooleate, Span 80) was mixed with a lipid (1,2-dioleoyl-sn-glycero-3-phosphocholine, PC), whose adsorption rate on the droplet surface and saturated interfacial tension were lower than those of Span 80. By changing the surfactant composition, we established the conditions under which the droplets initially form a honeycomb pattern and subsequently adhere to each other via DIB formation to minimize the interfacial energy. In addition, the reconstituted membrane protein nanopores at the DIBs were able to transport molecules. This new method, using the difference in the adsorption rates of two surfactants, allows the formation of a honeycomb pattern of DIB-bounded droplets in a single step, and thus facilitates research using DIB-bounded droplet assemblies.
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Castillo-Sánchez, José Carlos, Nuria Roldán, Begoña García-Álvarez, Emma Batllori, Alberto Galindo, Antonio Cruz, and Jesús Pérez-Gil. "The highly packed and dehydrated structure of preformed unexposed human pulmonary surfactant isolated from amniotic fluid." American Journal of Physiology-Lung Cellular and Molecular Physiology 322, no. 2 (February 1, 2022): L191—L203. http://dx.doi.org/10.1152/ajplung.00230.2021.
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By coating the alveolar air-liquid interface, lung surfactant overwhelms surface tension forces that, otherwise, would hinder the lifetime effort of breathing. Years of research have provided a picture of how highly hydrophobic and specialized proteins in surfactant promote rapid and efficient formation of phospholipid-based complex three-dimensional films at the respiratory surface, highly stable under the demanding breathing mechanics. However, recent evidence suggests that the structure and performance of surfactant typically isolated from bronchoalveolar lung lavages may be far from that of nascent, still unused, surfactant as freshly secreted by type II pneumocytes into the alveolar airspaces. In the present work, we report the isolation of lung surfactant from human amniotic fluid (amniotic fluid surfactant, AFS) and a detailed description of its composition, structure, and surface activity in comparison to a natural surfactant (NS) purified from porcine bronchoalveolar lavages. We observe that the lipid/protein complexes in AFS exhibit a substantially higher lipid packing and dehydration than in NS. AFS shows melting transitions at higher temperatures than NS and a conspicuous presence of nonlamellar phases. The surface activity of AFS is not only comparable with that of NS under physiologically meaningful conditions but displays significantly higher resistance to inhibition by serum or meconium, agents that inactivate surfactant in the context of severe respiratory pathologies. We propose that AFS may be the optimal model to study the molecular mechanisms sustaining pulmonary surfactant performance in health and disease, and the reference material to develop improved therapeutic surfactant preparations to treat yet unresolved respiratory pathologies.
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Batenburg, J. J., B. C. Ossendorp, G. T. Snoek, K. W. A. Wirtz, M. Houweling, and R. H. Elfring. "Phospholipid-transfer proteins and their mRNAs in developing rat lung and in alveolar type-II cells." Biochemical Journal 298, no. 1 (February 15, 1994): 223–29. http://dx.doi.org/10.1042/bj2980223.
Full textAbstract:
Gene expression of non-specific lipid-transfer protein (nsL-TP; identical with sterol carrier protein 2) and phosphatidylinositol-transfer protein (PI-TP) was investigated in developing rat lung. During the late prenatal period (between days 17 and 22) there is a 7-fold increase in the level of nsL-TP and a 2-fold rise in that of PI-TP. The prenatal increases in the levels of nsL-TP and PI-TP are accompanied by parallel increases in the levels of their mRNAs, indicating pretranslational regulation. Compared with whole lung, isolated alveolar type-II cells are enriched in nsL-TP and its mRNA, but not in PI-TP and its mRNA. The observation that the levels of nsL-TP and its mRNA in rat lung show a pronounced increase in the period of accelerated surfactant formation, together with the observation that the surfactant-producing type-II cells are enriched in nsL-TP and its mRNA, suggest that nsL-TP plays a role in the metabolism of pulmonary surfactant.
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Haddad, I. Y., J. P. Crow, P. Hu, Y. Ye, J. Beckman, and S. Matalon. "Concurrent generation of nitric oxide and superoxide damages surfactant protein A." American Journal of Physiology-Lung Cellular and Molecular Physiology 267, no. 3 (September 1, 1994): L242—L249. http://dx.doi.org/10.1152/ajplung.1994.267.3.l242.
Full textAbstract:
The conditions under which nitric oxide (.NO) may modulate or promote lung injury have not been identified. We hypothesized that .NO-induced injury results from peroxynitrite, formed by the reaction of .NO with superoxide. The simultaneous generation of .NO and superoxide by 3-morpholinosydnonimine (SIN-1, 0.1-2 mM) resulted in oxidation of dihydrorhodamine, a marker of peroxynitrite production, and a dose-dependent decrease in the ability of SP-A to enhance lipid aggregation. Western blot analysis of SIN-1 exposed SP-A samples, overlaid with a polyclonal antibody against nitrotyrosine, were consistent with nitration of SP-A tyrosine residues. Superoxide dismutase (100 U/ml), L-cysteine (5 mM), xanthine oxidase (10 mU/ml) and xanthine (500 microM), or urate (100 microM) prevented the SIN-1-induced dihydrorhodamine oxidation and injury to SP-A. .NO alone, generated by S-nitroso-N-acetylpenicillamine plus 100 microM L-cysteine, or superoxide and hydrogen peroxide, generated by pterin and xanthine oxidase in the absence of iron, did not damage SP-A or oxidize dihydrorhodamine. We concluded that peroxynitrite, but not .NO or superoxide and hydrogen peroxide, in concentrations likely to be encountered in vivo, caused nitrotyrosine formation and decreased the ability of SP-A to aggregate lipids.
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Baoukina, Svetlana, and D. Peter Tieleman. "Lung Surfactant Protein SP-B Promotes Formation of Bilayer Reservoirs from Monolayer and Lipid Transfer between the Interface and Subphase." Biophysical Journal 100, no. 7 (April 2011): 1678–87. http://dx.doi.org/10.1016/j.bpj.2011.02.019.
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Numata, Mari, Satria Sajuthi, Yury A. Bochkov, Jessica Loeffler, Jamie Everman, Eszter K. Vladar, Riley A. Cooney, et al. "Anionic Pulmonary Surfactant Lipid Treatment Inhibits Rhinovirus A Infection of the Human Airway Epithelium." Viruses 15, no. 3 (March 14, 2023): 747. http://dx.doi.org/10.3390/v15030747.
Full textAbstract:
Rhinoviruses (RVs) are major instigators of acute exacerbations of asthma, COPD, and other respiratory diseases. RVs are categorized into three species (RV-A, RV-B, and RV-C), which comprise more than 160 serotypes, making it difficult to develop an effective vaccine. Currently, no effective treatment for RV infection is available. Pulmonary surfactant is an extracellular complex of lipids and proteins that plays a central role in regulating innate immunity in the lung. The minor pulmonary surfactant lipids, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI), are potent regulators of inflammatory processes and exert antiviral activity against respiratory syncytial virus (RSV) and influenza A viruses (IAV). In the current study, we examined the potencies of POPG and PI against rhinovirus A16 (RV-A16) in primary human airway epithelial cells (AECs) differentiated at an air–liquid interface (ALI). After AECs were infected with RV-A16, PI reduced the viral RNA copy number by 70% and downregulated (55–75%) the expression of antiviral (MDA5, IRF7, and IFN-lambda) and CXCL11 chemokine genes. In contrast, POPG only slightly decreased MDA5 (24%) and IRF7 (11%) gene expression but did not inhibit IFN-lambda gene expression or RV-A16 replication in AECs. However, both POPG and PI inhibited (50–80%) IL6 gene expression and protein secretion and CXCL11 protein secretion. PI treatment dramatically attenuated global gene expression changes induced by RV-A16 infection alone in AECs. The observed inhibitory effects were indirect and resulted mainly from the inhibition of virus replication. Cell-type enrichment analysis of viral-regulated genes opposed by PI treatment revealed the PI-inhibited viral induction of goblet cell metaplasia and the virus-induced downregulation of ciliated, club, and ionocyte cell types. Notably, the PI treatment also altered the ability of RV-A16 to regulate the expression of some phosphatidylinositol 4-kinase (PI4K); acyl-CoA-binding, domain-containing (ACBD); and low-density lipoprotein receptor (LDLR) genes that play critical roles in the formation and functioning of replication organelles (ROs) required for RV replication in host cells. These data suggest PI can be used as a potent, non-toxic, antiviral agent for RV infection prophylaxis and treatment.
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Tso, P., and J. A. Balint. "Formation and transport of chylomicrons by enterocytes to the lymphatics." American Journal of Physiology-Gastrointestinal and Liver Physiology 250, no. 6 (June 1, 1986): G715—G726. http://dx.doi.org/10.1152/ajpgi.1986.250.6.g715.
Full textAbstract:
Digestion of triglyceride in the intestine results in the production of 2-monoglyceride and fatty acid. Phosphatidylcholine is hydrolyzed in the lumen to form lysophosphatidylcholine before its absorption. These digestion products are absorbed by the enterocytes through simple diffusion. In contrast, cholesterol absorption seems specific and is energy dependent. After entry into the enterocytes, these lipid digestion products migrate to the endoplasmic reticulum. Both fatty acid-binding protein and sterol carrier protein may be involved in the intracellular transport of fatty acid and cholesterol, respectively. Through predominantly the monoglyceride pathway, monoglycerides and fatty acids are resynthesized to form triglyceride in the endoplasmic reticulum. The lipid droplets, coated with cholesterol, phospholipid, and apolipoproteins, are then further processed in the Golgi apparatus before being released by the enterocytes through exocytosis. As yet, little is known of the factors regulating the formation and release of these chylomicrons by the enterocytes. Although apolipoprotein B is a prerequisite for the formation of chylomicrons, the question of whether its supply is rate limiting for chylomicron formation remains to be demonstrated. Other factors that may play a role in chylomicron formation are luminal phospholipid supply, Ca2+, and microtubules. Chylomicrons and very low-density lipoproteins are probably produced by the enterocytes via different pathways. For example, Pluronic L-81, a hydrophobic surfactant, affects only chylomicron formation and has little effect on very low-density lipoprotein production. The movement of chylomicrons from the intercellular space through the basement membrane to the lamina propria is not fully understood. Once inside the lamina propria, the movement of chylomicrons is probably by diffusion and is greatly facilitated by interstitial hydration; thus the lymphogogic effect of fat absorption may serve an important function for the transfer of chylomicrons from the enterocytes to the lacteal.
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Hills, Brian A. "Role of Surfactant in Peritoneal Dialysis." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 20, no. 5 (September 2000): 503–15. http://dx.doi.org/10.1177/089686080002000505.
Full textAbstract:
Evidence is reviewed that demonstrates how the mesothelial cell in the normal peritoneum and comparable serosal cavities secretes surface-active phospholipid (SAPL) as a means of protecting itself and the membrane it forms with its neighbors. It is shown how SAPL, if adsorbed (reversibly bound) to mesothelium, can impart excellent lubricity, antiwear and release (antistick) properties, while impeding surgical adhesion formation. More-speculative benefits include acting as a deterrent to fibrosis and as a barrier to both protein leakage and pathogen invasion by spanning cell junctions. Such spanning would also “pin down” cell corners, impeding peeling as the first step in exfoliation encountered in prolonged continuous ambulatory peritoneal dialysis (CAPD). The molecular mechanism underlying each of these possible functions is adsorption. Morphological and hydrophobicity studies are discussed as validation for such an adsorbed lining and how it can be fortified by administering exogenous SAPL. Any role for SAPL in ultrafiltration is much more controversial. However, a surfactant lining can explain the very high permeability of the membrane to lipid-soluble drugs, implying that it is a barrier to water-soluble solutes. The clinical and animal evidence is conflicting but would seem to be best explained by a role for the barrier in promoting semipermeability, and hence the osmotic driving force for water transmission. Thus, adsorption of exogenous SAPL in CAPD patients with low ultrafiltration seems to restore this barrier function. The future direction for surfactant in CAPD would seem to rest with the physical chemists in producing formulations that optimize adsorption, probably involving a compromise between water solubility and surface activity of the phospholipids selected. It might even warrant using the interdialytic interval for re-adsorbing SAPL without the problem of dilution by a large volume of dialysate.
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Nag, Kaushik, James G. Munro, Kevin Inchley, Samuel Schürch, Nils O. Petersen, and Fred Possmayer. "SP-B refining of pulmonary surfactant phospholipid films." American Journal of Physiology-Lung Cellular and Molecular Physiology 277, no. 6 (December 1, 1999): L1179—L1189. http://dx.doi.org/10.1152/ajplung.1999.277.6.l1179.
Full textAbstract:
Pulmonary surfactant stabilizes the alveoli by lining the air-fluid interface with films that reduce surface tension to near 0 mN/m (γmin). Surfactant protein B (SP-B) enhances the surface activity of surfactant phospholipids. A captive bubble tensiometer (CBT) was used to study the properties of adsorbed films of dipalmitoylphosphatidylcholine (DPPC) with acidic 1-palmitoyl-2-oleoyl- sn-glycero-3-[phospho- rac-(1-glycerol)] (POPG) or neutral 1-palmitoyl-2-oleoyl- sn-glycerol-3-phosphocholine with (7:3) and without 1% dimeric SP-B. SP-B enhanced the adsorption rate of DPPC-containing neutral or acidic lipid suspensions (1 mg/ml) to a similar extent. Quasi-static cycling of these films revealed that SP-B significantly decreased the film area reduction required to reach γmin for the acidic but not for the neutral system. The results obtained with DPPC-phosphatidylglycerol (PG)-SP-B were consistent with selective DPPC adsorption into the surface monolayer during film formation. Film area reduction required to reach γmin with this system (with and without calcium) approached that of pure DPPC, suggesting selective DPPC insertion and PG squeeze-out. Dynamic cycling of such films showed that larger film area reductions were required to reach γmin for the neutral than for acidic system, even after 20 cycles. Fluorescence microscopy of solvent-spread DPPC-POPG-SP-B planar films revealed highly condensed structures at ∼25 mN/m, although no specific PG phase-segregated structures could be identified. The study suggests that specific interactions of SP-B with acidic phospholipids of surfactant may be involved in the generation and maintenance of DPPC-rich films in the alveoli.
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Nicholls, Hayley T., Jason L. Hornick, and David E. Cohen. "Phosphatidylcholine transfer protein/StarD2 promotes microvesicular steatosis and liver injury in murine experimental steatohepatitis." American Journal of Physiology-Gastrointestinal and Liver Physiology 313, no. 1 (July 1, 2017): G50—G61. http://dx.doi.org/10.1152/ajpgi.00379.2016.
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Mice fed a methionine- and choline-deficient (MCD) diet develop steatohepatitis that recapitulates key features of nonalcoholic steatohepatitis (NASH) in humans. Phosphatidylcholine is the most abundant phospholipid in the surfactant monolayer that coats and stabilizes lipid droplets within cells, and choline is required for its major biosynthetic pathway. Phosphatidylcholine-transfer protein (PC-TP), which exchanges phosphatidylcholines among membranes, is enriched in hepatocytes. PC-TP also regulates fatty acid metabolism through interactions with thioesterase superfamily member 2. We investigated the contribution of PC-TP to steatohepatitis induced by the MCD diet. Pctp−/− and wild-type control mice were fed the MCD diet for 5 wk and were then euthanized for histopathologic and biochemical analyses, as well as determinations of mRNA and protein expression. Whereas all mice developed steatohepatitis, plasma alanine aminotransferase and aspartate aminotransferase activities were only elevated in wild-type mice, indicating that Pctp−/− mice were protected from MCD diet-induced hepatocellular injury. Reduced hepatotoxicity due to the MCD diet in the absence of PC-TP expression was further evidenced by decreased activation of c-Jun and reduced plasma concentrations of fibroblast growth factor 21. Despite similar total hepatic concentrations of phosphatidylcholines and other lipids, the relative abundance of microvesicular lipid droplets within hepatocytes was reduced in Pctp−/− mice. Considering that the formation of larger lipid droplets may serve to protect against lipotoxicity in NASH, our findings suggest a pathogenic role for PC-TP that could be targeted in the management of this condition. NEW & NOTEWORTHY Phosphatidylcholine-transfer protein (PC-TP) is a highly specific phosphatidylcholine-binding protein that we previously showed to regulate hepatocellular nutrient metabolism through its interacting partner thioesterase superfamily member 2 (Them2). This study identifies a pathogenic role for PC-TP, independent of Them2, in the methionine- and choline-deficient diet model of experimental steatohepatitis. Our current observations suggest that PC-TP promotes liver injury by mediating the intermembrane transfer of phosphatidylcholines, thus stabilizing more pathogenic microvesicular lipid droplets.
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Liu, Siyu, Tianyu Wei, Hongyun Lu, Xiayu Liu, Ying Shi, and Qihe Chen. "Interactions between Mannosylerythritol Lipid-A and Heat-Induced Soy Glycinin Aggregates: Physical and Chemical Characteristics, Functional Properties, and Structural Effects." Molecules 27, no. 21 (October 31, 2022): 7393. http://dx.doi.org/10.3390/molecules27217393.
Full textAbstract:
Protein-surfactant interactions have a significant influence on food functionality, which has attracted increasing attention. Herein, the effect of glycolipid mannosylerythritol lipid-A (MEL-A) on the heat-induced soy glycinin (11S) aggregates was investigated by measuring the structure, binding properties, interfacial behaviors, and emulsification characteristics of the aggregates. The results showed that MEL-A led to a decrease in the surface tension, viscoelasticity, and foaming ability of the 11S aggregates. In addition, MEL-A with a concentration above critical micelle concentration (CMC) reduced the random aggregation of 11S protein after heat treatment, thus facilitating the formation of self-assembling core-shell particles composed of a core of 11S aggregates covered by MEL-A shells. Infrared spectroscopy, circular dichroism spectroscopy, fluorescence spectroscopy, and isothermal titration calorimetry also confirmed that the interaction forces between MEL-A and 11S were driven by hydrophobic interactions between the exposed hydrophobic groups of the protein and the fatty acid chains or acetyl groups of MEL-A, as well as the hydrogen bonding between mannosyl-D-erythritol groups of MEL-A and amino acids of 11S. The findings of this study indicated that such molecular interactions are responsible for the change in surface behavior and the enhancement of foaming stability and emulsifying property of 11S aggregates upon heat treatment.
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Yao, Li-Juan, Carol Richardson, Carol Ford, N. Mathialagan, George Mackie, Geoffrey L. Hammond, Paul G. R. Harding, and Fred Possmayer. "Expression of mature pulmonary surfactant-associated protein B (SP-B) in Escherichia coli using truncated human SP-B cDNAs." Biochemistry and Cell Biology 68, no. 2 (February 1, 1990): 559–66. http://dx.doi.org/10.1139/o90-080.
Full textAbstract:
The present communication documents attempts to produce the mature form of human surfactant-associated protein B (SP-B) by modification of the 5′ and 3′ regions of the cDNA and expression of the truncated cDNAs after insertion into the vector pKK223-3. The 5′ end of a cDNA for human SP-B (1407 base pairs) was reconstructed through the ligation of synthetic oligonucleotides to an internal PstI site in the 5′ region. This construction coded for the initiation of protein synthesis at a Met codon adjacent to a codon for the N-terminal Phe of the mature polypeptide. Variable amounts of the 3′ end of the human SP-B cDNA were deleted with mung bean nuclease and exonuclease III. The resulting blunt-ended 3′ fragments were then ligated to a synthetic oligonucleotide linker designed to create a stop codon. The modified 5′ and 3′ ends were ligated to a short PstI-BamHI fragment isolated from the SP-B cDNA and inserted into the expression vector pKK223-3. In vitro translation of sense mRNAs derived from the truncated SP-B cDNAs yielded oligopeptides of appropriate molecular weights, as indicated by urea – sodium dodecyl sulphate –polyacrylamide gel electrophoresis of either intact or immunoprecipitated reaction mixtures. Expression of SP-B in Escherichia coli was confirmed by Northern blot analysis for the mRNAs corresponding to the truncated cDNAs in appropriately transformed bacteria induced with the galactose analog isopropyl-β-thiogalactoside. Western blot analysis using rabbit antisera prepared against bovine SP-B confirmed the presence of mature SP-B in lipid extracts of transformed E. coli, but the amounts were very small. These studies demonstrate the feasibility of producing mature human SP-B through recombinant DNA technology, but indicate that it may be necessary to use a fusion protein approach to obtain sufficient amounts for the formation of artificial pulmonary surfactant.Key words: pulmonary surfactant (human), hydrophobic proteins, artificial pulmonary surfactant, in vitro translation.
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Rüstow, B., I. Kolleck, F. Guthmann, R. Haupt, D. Kunze, and P. Stevens. "Synthesis and secretion of plasmalogens by type-II pneumocytes." Biochemical Journal 302, no. 3 (September 15, 1994): 665–68. http://dx.doi.org/10.1042/bj3020665.
Full textAbstract:
Alveolar surfactant (exposed to air and therefore a prime target of air oxidants) is supplied with antioxidants during its intracellular formation on type-II pneumocytes [Rüstow, Haupt, Stevens and Kunze (1993) Am. J. Physiol. 265, L133-L139]. Plasmalogens can protect animal cells against lipid peroxidation caused by u.v. radiation. It has been suggested that plasmalogens play a direct role in protecting animal cell membranes against oxidative stress [Zoeller, Morand and Raetz (1988) J. Biol. Chem. 263, 11590-11596]. We investigated biosynthesis and secretion of plasmalogens and phospholipids by type-II cells of adult rat lungs. The plasmalogens of type-II cells consist of 93% ethanolamine plasmalogens (EthPlas) and 7% choline plasmalogens (ChoPlas). Plasmalogens isolated from alveolar surfactant, however, consist of 36.5% ChoPlas and 63.5% EthPlas. The different incorporation rates of [14C]hexadecanol into both types of plasmalogen by type-II pneumocytes are reflected in the relative proportions of their total cellular plasmalogen content. Type-II cells cultured in the presence of labelled hexadecanol or labelled hexadecylglycerol and of labelled palmitate secrete labelled ChoPlas and labelled phospholipids, both spontaneously and in response to isoprenaline. The spontaneous and stimulated secretion rates of labelled ChoPlas are 3-6 times higher than those of labelled EthPlas. This higher relative secretion rate of ChoPlas corresponds to its higher proportion in the total plasmalogen content of alveolar surfactant compared with type-II cells. Added extracellular surfactant-specific protein A inhibits the secretion of plasmalogens as well as that of phospholipids by type-II cells. The molecular species of EthPlas and ChoPlas isolated from type-II cells or lung lavage do not differ significantly and consist mainly of molecular species containing poly-unsaturated fatty acids. We conclude that ChoPlas are secreted partly as integral constituents of the alveolar surfactant. Type-II cells select between both types of plasmalogens for secretion as a constituent of surfactant. The intramolecular sorting signal presumably is the choline moiety.
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Moghieb, Ahmed, Geremy Clair, Hugh D. Mitchell, Joseph Kitzmiller, Erika M. Zink, Young-Mo Kim, Vladislav Petyuk, et al. "Time-resolved proteome profiling of normal lung development." American Journal of Physiology-Lung Cellular and Molecular Physiology 315, no. 1 (July 1, 2018): L11—L24. http://dx.doi.org/10.1152/ajplung.00316.2017.
Full textAbstract:
Biochemical networks mediating normal lung morphogenesis and function have important implications for ameliorating morbidity and mortality in premature infants. Although several transcript-level studies have examined normal lung development, corresponding protein-level analyses are lacking. Here we performed proteomics analysis of murine lungs from embryonic to early adult ages to identify the molecular networks mediating normal lung development. We identified 8,932 proteins, providing a deep and comprehensive view of the lung proteome. Analysis of the proteomics data revealed discrete modules and the underlying regulatory and signaling network modulating their expression during development. Our data support the cell proliferation that characterizes early lung development and highlight responses of the lung to exposure to a nonsterile oxygen-rich ambient environment and the important role of lipid (surfactant) metabolism in lung development. Comparison of dynamic regulation of proteomic and recent transcriptomic analyses identified biological processes under posttranscriptional control. Our study provides a unique proteomic resource for understanding normal lung formation and function and can be freely accessed at Lungmap.net.
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Parra, Elisa, Lara H. Moleiro, Ivan López-Montero, Antonio Cruz, Francisco Monroy, and Jesús Pérez-Gil. "A combined action of pulmonary surfactant proteins SP-B and SP-C modulates permeability and dynamics of phospholipid membranes." Biochemical Journal 438, no. 3 (August 26, 2011): 555–64. http://dx.doi.org/10.1042/bj20110681.
Full textAbstract:
Proteins SP-B and SP-C are essential to promote formation of surface-active films at the respiratory interface, but their mechanism of action is still under investigation. In the present study we have analysed the effect of the proteins on the accessibility of native, quasi-native and model surfactant membranes to incorporation of the fluorescent probes Nile Red (permeable) and FM 1-43 (impermeable) into membranes. We have also analysed the effect of single or combined proteins on membrane permeation using the soluble fluorescent dye calcein. The fluorescence of FM 1-43 was always higher in membranes containing SP-B and/or SP-C than in protein-depleted membranes, in contrast with Nile Red which was very similar in all of the materials tested. SP-B and SP-C promoted probe partition with markedly different kinetics. On the other hand, physiological proportions of SP-B and SP-C caused giant oligolamellar vesicles to incorporate FM 1-43 from the external medium into apparently most of the membranes instantaneously. In contrast, oligolamellar pure lipid vesicles appeared to be mainly labelled in the outermost membrane layer. Pure lipidic vesicles were impermeable to calcein, whereas it permeated through membranes containing SP-B and/or SP-C. Vesicles containing only SP-B were stable, but prone to vesicle–vesicle interactions, whereas those containing only SP-C were extremely dynamic, undergoing frequent fluctuations and ruptures. Differential structural effects of proteins on vesicles were confirmed by electron microscopy. These results suggest that SP-B and SP-C have different contributions to inter- and intra-membrane lipid dynamics, and that their combined action could provide unique effects to modulate structure and dynamics of pulmonary surfactant membranes and films.
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Zhu, Kun, and Charles O. Rock. "RhlA Converts β-Hydroxyacyl-Acyl Carrier Protein Intermediates in Fatty Acid Synthesis to the β-Hydroxydecanoyl-β-Hydroxydecanoate Component of Rhamnolipids in Pseudomonas aeruginosa." Journal of Bacteriology 190, no. 9 (March 7, 2008): 3147–54. http://dx.doi.org/10.1128/jb.00080-08.
Full textAbstract:
ABSTRACT Pseudomonas aeruginosa secretes a rhamnolipid (RL) surfactant that functions in hydrophobic nutrient uptake, swarming motility, and pathogenesis. We show that RhlA supplies the acyl moieties for RL biosynthesis by competing with the enzymes of the type II fatty acid synthase (FASII) cycle for the β-hydroxyacyl-acyl carrier protein (ACP) pathway intermediates. Purified RhlA forms one molecule of β-hydroxydecanoyl-β-hydroxydecanoate from two molecules of β-hydroxydecanoyl-ACP and is the only enzyme required to generate the lipid component of RL. The acyl groups in RL are primarily β-hydroxydecanoyl, and in vitro, RhlA has a greater affinity for 10-carbon substrates, illustrating that RhlA functions as a molecular ruler that selectively extracts 10-carbon intermediates from FASII. Eliminating either FabA or FabI activity in P. aeruginosa increases RL production, illustrating that slowing down FASII allows RhlA to more-effectively compete for β-hydroxydecanoyl-ACP. In Escherichia coli, the rate of fatty acid synthesis increases 1.3-fold when RhlA is expressed, to ensure the continued formation of fatty acids destined for membrane phospholipid even though 24% of the carbon entering FASII is diverted to RL synthesis. Previous studies have placed a ketoreductase, called RhlG, before RhlA in the RL biosynthetic pathway; however, our experiments show that RhlG has no role in RL biosynthesis. We conclude that RhlA is necessary and sufficient to form the acyl moiety of RL and that the flux of carbon through FASII accelerates to support RL production and maintain a supply of acyl chains for phospholipid synthesis.
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Burrows, S. M., O. Ogunro, A. A. Frossard, L. M. Russell, P. J. Rasch, and S. Elliott. "A physically-based framework for modelling the organic fractionation of sea spray aerosol from bubble film Langmuir equilibria." Atmospheric Chemistry and Physics Discussions 14, no. 5 (March 3, 2014): 5375–443. http://dx.doi.org/10.5194/acpd-14-5375-2014.
Full textAbstract:
Abstract. The presence of a large fraction of organic matter in primary sea spray aerosol (SSA) can strongly affect its cloud condensation nuclei activity and interactions with marine clouds. Global climate models require new parameterizations of the SSA composition in order to improve the representation of these processes. Existing proposals for such a parameterization use remotely-sensed chlorophyll a concentrations as a proxy for the biogenic contribution to the aerosol. However, both observations and theoretical considerations suggest that existing relationships with chlorophyll a, derived from observations at only a few locations, may not be representative for all ocean regions. We introduce a novel framework for parameterizing the fractionation of marine organic matter into SSA based on a competitive Langmuir adsorption equilibrium at bubble surfaces. Marine organic matter is partitioned into classes with differing molecular weights, surface excesses, and Langmuir adsorption parameters. The classes include a lipid-like mixture associated with labile dissolved organic carbon (DOC), a polysaccharide-like mixture associated primarily with semi-labile DOC, a protein-like mixture with concentrations intermediate between lipids and polysaccharides, a processed mixture associated with recalcitrant surface DOC, and a deep abyssal humic-like mixture. Box model calculations have been performed for several cases of organic adsorption to illustrate the underlying concepts. We then apply the framework to output from a global marine biogeochemistry model, by partitioning total dissolved organic carbon into several classes of macromolecules. Each class is represented by model compounds with physical and chemical properties based on existing laboratory data. This allows us to globally map the predicted organic mass fraction of the nascent submicron sea spray aerosol. Predicted relationships between chlorophyll a and organic fraction are similar to existing empirical parameterizations, but can vary between biologically productive and non-productive regions, and seasonally within a given region. Major uncertainties include the bubble film thickness at bursting and the variability of organic surfactant activity in the ocean, which is poorly constrained. In addition, polysaccharides may enter the aerosol more efficiently than Langmuir adsorption would suggest. Potential mechanisms for include the formation of marine colloidal particles that may be more efficiently swept up by rising particles, and cooperative adsorption of polysaccharides with proteins or lipids. These processes may make important contributions to the aerosol, but are not included here. This organic fractionation framework is an initial step towards a closer linking of ocean biogeochemistry and aerosol chemical composition in Earth system models. Future work should focus on improving constraints on model parameters through new laboratory experiments or through empirical fitting to observed relationships in the real ocean and atmosphere, as well as on atmospheric implications of the variable composition of organic matter in sea spray.
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Burrows, S. M., O. Ogunro, A. A. Frossard, L. M. Russell, P. J. Rasch, and S. M. Elliott. "A physically based framework for modeling the organic fractionation of sea spray aerosol from bubble film Langmuir equilibria." Atmospheric Chemistry and Physics 14, no. 24 (December 19, 2014): 13601–29. http://dx.doi.org/10.5194/acp-14-13601-2014.
Full textAbstract:
Abstract. The presence of a large fraction of organic matter in primary sea spray aerosol (SSA) can strongly affect its cloud condensation nuclei activity and interactions with marine clouds. Global climate models require new parameterizations of the SSA composition in order to improve the representation of these processes. Existing proposals for such a parameterization use remotely sensed chlorophyll a concentrations as a proxy for the biogenic contribution to the aerosol. However, both observations and theoretical considerations suggest that existing relationships with chlorophyll a, derived from observations at only a few locations, may not be representative for all ocean regions. We introduce a novel framework for parameterizing the fractionation of marine organic matter into SSA based on a competitive Langmuir adsorption equilibrium at bubble surfaces. Marine organic matter is partitioned into classes with differing molecular weights, surface excesses, and Langmuir adsorption parameters. The classes include a lipid-like mixture associated with labile dissolved organic carbon (DOC), a polysaccharide-like mixture associated primarily with semilabile DOC, a protein-like mixture with concentrations intermediate between lipids and polysaccharides, a processed mixture associated with recalcitrant surface DOC, and a deep abyssal humic-like mixture. Box model calculations have been performed for several cases of organic adsorption to illustrate the underlying concepts. We then apply the framework to output from a global marine biogeochemistry model, by partitioning total dissolved organic carbon into several classes of macromolecules. Each class is represented by model compounds with physical and chemical properties based on existing laboratory data. This allows us to globally map the predicted organic mass fraction of the nascent submicron sea spray aerosol. Predicted relationships between chlorophyll a and organic fraction are similar to existing empirical parameterizations, but can vary between biologically productive and nonproductive regions, and seasonally within a given region. Major uncertainties include the bubble film thickness at bursting, and the variability of organic surfactant activity in the ocean, which is poorly constrained. In addition, polysaccharides may enter the aerosol more efficiently than Langmuir adsorption would suggest. Potential mechanisms for enrichment of polysaccharides in sea spray include the formation of marine colloidal particles that may be more efficiently swept up by rising bubbles, and cooperative adsorption of polysaccharides with proteins or lipids. These processes may make important contributions to the aerosol, but are not included here. This organic fractionation framework is an initial step towards a closer linking of ocean biogeochemistry and aerosol chemical composition in Earth system models. Future work should focus on improving constraints on model parameters through new laboratory experiments or through empirical fitting to observed relationships in the real ocean and atmosphere, as well as on atmospheric implications of the variable composition of organic matter in sea spray.
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Gref, R., C. Deloménie, A. Maksimenko, E. Gouadon, G. Percoco, E. Lati, D. Desmaële, F. Zouhiri, and P. Couvreur. "Vitamin C–squalene bioconjugate promotes epidermal thickening and collagen production in human skin." Scientific Reports 10, no. 1 (October 9, 2020). http://dx.doi.org/10.1038/s41598-020-72704-1.
Full textAbstract:
Abstract Vitamin C (Vit C) benefits to human skin physiology notably by stimulating the biosynthesis of collagen. The main cutaneous collagens are types I and III, which are less synthesized with aging. Vit C is one of the main promotors of collagen formation but it poorly bypasses the epidermis stratum corneum barrier. To address this challenge, we developed a lipophilic version of Vit C for improving skin diffusion and delivery. Vit C was covalently conjugated to squalene (SQ), a natural lipid of the skin, forming a novel Vit C–SQ derivative suitable for cream formulation. Its biological activity was investigated on human whole skin explants in an ex vivo model, through histology and protein and gene expression analyses. Results were compared to Vit C coupled to the reference lipophilic compound palmitic acid, (Vit C–Palmitate). It was observed that Vit C–SQ significantly increased epidermal thickness and preferentially favored collagen III production in human skin after application for 10 days. It also promoted glycosaminoglycans production in a higher extent comparatively to Vit C–Palmitate and free Vit C. Microdissection of the explants to separate dermis and epidermis allowed to measure higher transcriptional effects either in epidermis or in dermis. Among the formulations studied, the strongest effects were observed with Vit C–SQ.
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Harishchandra, Rakesh Kumar, Mohammed Saleem, and Hans-Joachim Galla. "Nanoparticle interaction with model lung surfactant monolayers." Journal of The Royal Society Interface 7, suppl_1 (October 21, 2009). http://dx.doi.org/10.1098/rsif.2009.0329.focus.
Full textAbstract:
One of the most important functions of the lung surfactant monolayer is to form the first line of defence against inhaled aerosols such as nanoparticles (NPs), which remains largely unexplored. We report here, for the first time, the interaction of polyorganosiloxane NPs (AmorSil20: 22 nm in diameter) with lipid monolayers characteristic of alveolar surfactant. To enable a better understanding, the current knowledge about an established model surface film that mimics the surface properties of the lung is reviewed and major results originating from our group are summarized. The pure lipid components dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol have been used to study the biophysical behaviour of their monolayer films spread at the air–water interface in the presence of NPs. Film balance measurements combined with video-enhanced fluorescence microscopy have been used to investigate the formation of domain structures and the changes in the surface pattern induced by NPs. We are able to show that NPs are incorporated into lipid monolayers with a clear preference for defect structures at the fluid–crystalline interface leading to a considerable monolayer expansion and fluidization. NPs remain at the air–water interface probably by coating themselves with lipids in a self-assembly process, thereby exhibiting hydrophobic surface properties. We also show that the domain structure in lipid layers containing surfactant protein C, which is potentially responsible for the proper functioning of surfactant material, is considerably affected by NPs.
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Edwardson, Thomas G. W., Stephan Tetter, and Donald Hilvert. "Two-tier supramolecular encapsulation of small molecules in a protein cage." Nature Communications 11, no. 1 (October 26, 2020). http://dx.doi.org/10.1038/s41467-020-19112-1.
Full textAbstract:
Abstract Expanding protein design to include other molecular building blocks has the potential to increase structural complexity and practical utility. Nature often employs hybrid systems, such as clathrin-coated vesicles, lipid droplets, and lipoproteins, which combine biopolymers and lipids to transport a broader range of cargo molecules. To recapitulate the structure and function of such composite compartments, we devised a supramolecular strategy that enables porous protein cages to encapsulate poorly water-soluble small molecule cargo through templated formation of a hydrophobic surfactant-based core. These lipoprotein-like complexes protect their cargo from sequestration by serum proteins and enhance the cellular uptake of fluorescent probes and cytotoxic drugs. This design concept could be applied to other protein cages, surfactant mixtures, and cargo molecules to generate unique hybrid architectures and functional capabilities.
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Sabale, Vidya, Manjusha Charde, Nitin Dumore, and Ujwala Mahajan. "Recent development of Proniosomal Transdermal drug delivery: an Overview." Current Drug Delivery 19 (April 22, 2022). http://dx.doi.org/10.2174/1567201819666220422153059.
Full textAbstract:
Abstract: Proniosomes are the stable carriers used for Transdermal application as compared to other vesicular delivery systems like niosomes and liposomes. Oral administration of a drug is associated severe GIT irritation and first pass metabolism. Vesicular drug delivery system includes basic concept of niosomes and proniosomes which describe their mechanism of action, structural formation, interactive study with skin, composition, method of preparation. Gels contains high aqueous component as compared to ointment and creams, due to which it can dissolve high concentration of drugs, and thus helps the drug to migrate easily through a vehicle.th this respect gels are considered to be superior in terms of use and patient compliance. This review will focus on the up to date research development, which are applicable to various diseases by using of proniosomes. Proniosomes are prepared mainly by different concentrations of nonionic surfactant, cholesterol, lecithin by entrapping hydrophobic as well as hydrophilic drugs. In earlier studies it was found that the non ionic surfactants and phospholipids which provided higher penetration since it had been found that some phospholipids have the ability to fluidize the lipid bilayer of stratum corneum and diffused through them. In future, Proniosomes can gain more importance in the area of melanoma, brain targeting, protein and peptide drug delivery, gene delivery, hematological drug delivery and also in cosmetics, neutrceuticals.
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Sabale, Vidya, Manjusha Charde, Nitin Dumore, and Ujwala Mahajan. "Recent development of Proniosomal Transdermal drug delivery: an Overview." Current Drug Delivery 19 (April 22, 2022). http://dx.doi.org/10.2174/1567201819666220422153059.
Full textAbstract:
Abstract: Proniosomes are the stable carriers used for Transdermal application as compared to other vesicular delivery systems like niosomes and liposomes. Oral administration of a drug is associated severe GIT irritation and first pass metabolism. Vesicular drug delivery system includes basic concept of niosomes and proniosomes which describe their mechanism of action, structural formation, interactive study with skin, composition, method of preparation. Gels contains high aqueous component as compared to ointment and creams, due to which it can dissolve high concentration of drugs, and thus helps the drug to migrate easily through a vehicle.th this respect gels are considered to be superior in terms of use and patient compliance. This review will focus on the up to date research development, which are applicable to various diseases by using of proniosomes. Proniosomes are prepared mainly by different concentrations of nonionic surfactant, cholesterol, lecithin by entrapping hydrophobic as well as hydrophilic drugs. In earlier studies it was found that the non ionic surfactants and phospholipids which provided higher penetration since it had been found that some phospholipids have the ability to fluidize the lipid bilayer of stratum corneum and diffused through them. In future, Proniosomes can gain more importance in the area of melanoma, brain targeting, protein and peptide drug delivery, gene delivery, hematological drug delivery and also in cosmetics, neutrceuticals.
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Van Khanh, Nguyen, Vu Van Thuong, Nguyen Thanh Hai, and Hoang Anh Tuan. "Preparation of Aspirin Nanosuspension by Antisolvent Precipitation Method." VNU Journal of Science: Medical and Pharmaceutical Sciences 37, no. 3 (September 14, 2021). http://dx.doi.org/10.25073/2588-1132/vnumps.4294.
Full textAbstract:
This study aims to enhance the dissolution rate of a poorly-soluble drug, aspirin, by fabricating aspirin nanosuspensions using the anti-solvent precipitation. The study investigates the effect of the type of solvents, solvent to anti-solvent ratio, drug concentration, machines, stirring speed, ultrasonication technique and the temperature of solvent on the particle size and polydispersity index. The characterization of the original aspirin powder and nanoparticles was evaluated by differential scanning calorimetry and in vitro dissolution test. The results indicate that the selected formulation showed the smallest mean size of 228.2 ± 24.6 nm and a zeta potential of - 40.3 ± 2.5 mV. The differential scanning calorimetry analysis demonstrates that aspirin nanoparticles possessed lower crystallinity than the raw aspirin powder. The dissolution of nanoparticle was significantly higher compared with the original drug in the in vitro dissolution test.
Keywords: Aspirin, nanosuspension, anti-solvent precipitation, differential scanning calorimetry, dissolution.
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