scholarly journals Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

2017 ◽  
Vol 114 (18) ◽  
pp. E3592-E3601 ◽  
Author(s):  
Jenny Marie Andersson ◽  
Carl Grey ◽  
Marcus Larsson ◽  
Tiago Mendes Ferreira ◽  
Emma Sparr
Keyword(s):  
Molecular Structure ◽  
Self Assembly ◽  
Lung Surfactant ◽  
Dry Weight ◽  
Isotopic Labeling ◽  
Lamellar Phase ◽  
Large Set ◽  
Clinical Grade ◽  
Surfactant Mixtures ◽  
Protein Film

The lipid–protein film covering the interface of the lung alveolar in mammals is vital for proper lung function and its deficiency is related to a range of diseases. Here we present a molecular-level characterization of a clinical-grade porcine lung surfactant extract using a multitechnique approach consisting ofH1–C13solid-state nuclear magnetic spectroscopy, small- and wide-angle X-ray scattering, and mass spectrometry. The detailed characterization presented for reconstituted membranes of a lung extract demonstrates that the molecular structure of lung surfactant strongly depends on the concentration of cholesterol. If cholesterol makes up about 11% of the total dry weight of lung surfactant, the surfactant extract adopts a single liquid-ordered lamellar phase,Lα(o), at physiological temperatures. ThisLα(o)phase gradually changes into a liquid-disordered lamellar phase,Lα(d), when the temperature is increased by a few degrees. In the absence of cholesterol the system segregates into one lamellar gel phase and oneLα(d)phase. Remarkably, it was possible to measure a large set of order parameter magnitudes|SCH|from the liquid-disordered and -ordered lamellar phases and assign them to specific C–H bonds of the phospholipids in the biological extract with no use of isotopic labeling. These findings with molecular details on lung surfactant mixtures together with the presented NMR methodology may guide further development of pulmonary surfactant pharmaceuticals that better mimic the physiological self-assembly compositions for treatment of pathological states such as respiratory distress syndrome.

Impact of the Degree of Ethoxylation of the Ethoxylated Polysorbate Nonionic Surfactant on the Surface Self-Assembly of Hydrophobin-Ethoxylated Polysorbate Surfactant Mixtures

Langmuir ◽  
2014 ◽  
Vol 30 (32) ◽  
pp. 9741-9751 ◽  
Author(s):  
Jeffrey Penfold ◽  
Robert K. Thomas ◽  
Peixun Li ◽  
Jordan T. Petkov ◽  
Ian Tucker ◽  
...  
Keyword(s):  
Nonionic Surfactant ◽  
Self Assembly ◽  
Surfactant Mixtures

Inference of molecular structure for characterization and improvement of clinical grade immunocytokines

2021 ◽  
Vol 213 (1) ◽  
pp. 107696
Author(s):  
Tiziano Ongaro ◽  
Salvatore R. Guarino ◽  
Luigi Scietti ◽  
Martina Palamini ◽  
Sarah Wulhfard ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Clinical Grade

scholarly journals Exploring the in meso crystallization mechanism by characterizing the lipid mesophase microenvironment during the growth of single transmembrane α-helical peptide crystals

2016 ◽  
Vol 374 (2072) ◽  
pp. 20150125 ◽  
Author(s):  
Leonie van 't Hag ◽  
Konstantin Knoblich ◽  
Shane A. Seabrook ◽  
Nigel M. Kirby ◽  
Stephen T. Mudie ◽  
...  
Keyword(s):  
Crystal Growth ◽  
Self Assembly ◽  
Lamellar Phase ◽  
Cubic Phase ◽  
Supporting Evidence ◽  
X Ray ◽  
X Ray Scattering ◽  
Standard Procedures ◽  
Helical Peptide ◽  
Saxs Analysis

The proposed mechanism for in meso crystallization of transmembrane proteins suggests that a protein or peptide is initially uniformly dispersed in the lipid self-assembly cubic phase but that crystals grow from a local lamellar phase, which acts as a conduit between the crystal and the bulk cubic phase. However, there is very limited experimental evidence for this theory. We have developed protocols to investigate the lipid mesophase microenvironment during crystal growth using standard procedures readily available in crystallography laboratories. This technique was used to characterize the microenvironment during crystal growth of the DAP12-TM peptide using synchrotron small angle X-ray scattering (SAXS) with a micro-sized X-ray beam. Crystal growth was found to occur from the gyroid cubic mesophase. For one in four crystals, a highly oriented local lamellar phase was observed, providing supporting evidence for the proposed mechanism for in meso crystallization. A new observation of this study was that we can differentiate diffraction peaks from crystals grown in meso , from peaks originating from the surrounding lipid matrix, potentially opening up the possibility of high-throughput SAXS analysis of in meso grown crystals. This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.

scholarly journals Nanoparticle interaction with model lung surfactant monolayers

2009 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Rakesh Kumar Harishchandra ◽  
Mohammed Saleem ◽  
Hans-Joachim Galla
Keyword(s):  
Surface Properties ◽  
Self Assembly ◽  
Current Knowledge ◽  
Surface Film ◽  
Lung Surfactant ◽  
Hydrophobic Surface ◽  
Surface Pattern ◽  
Lipid Monolayers ◽  
Water Interface ◽  
Air Water Interface

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.

Interaction of surfactant mixtures with reactive oxygen and nitrogen species

1995 ◽  
Vol 78 (5) ◽  
pp. 1800-1805 ◽  
Author(s):  
J. Cifuentes ◽  
J. Ruiz-Oronoz ◽  
C. Myles ◽  
B. Nieves ◽  
W. A. Carlo ◽  
...  
Keyword(s):  
Lung Surfactant ◽  
Alveolar Epithelium ◽  
Reactive Species ◽  
Surfactant Mixtures ◽  
Surfactant Deficiency ◽  
High Lipid ◽  
Fenton Reagents ◽  
Protein Sulfhydryl ◽  
Nitrogen Reactive Species ◽  
Protein Sulfhydryl Groups

Increased concentrations of partially reduced oxygen and nitrogen reactive species damage the alveolar epithelium and either cause or exacerbate surfactant deficiency. For this reason, there is a quest to identify surfactant replacement mixtures, which in addition to repleting depleted surfactant stores can also reduce the steady-state concentrations of reactive species in the alveolar space. Herein, we evaluated the ability of natural lung surfactant (NLS) and two mixtures (Exosurf and Survanta) used clinically for the correction of surfactant deficiency to scavenge hydroxyl radical-type species (.OH), generated either by the decomposition of peroxynitrite or by Fenton reagents (FeCl3 + H2O2). Exosurf or Survanta decreased .OH only when present at high lipid concentrations (6.5 mM). On the other hand, 40 microM of NLS decreased .OH concentrations from 75 +/- 2 to 53 +/- 2 microM (P < 0.05), most likely because of the interaction of .OH with protein sulfhydryl groups. Similarly, 40 microM of NLS incubated with a bolus of H2O2 (400 microM) decreased the H2O2 concentration in the supernatant by approximately 50%, due to the presence of catalase-type activity. In contrast to NLS, neither Exosurf nor Survanta scavenged H2O2, even when present at millimolar lipid concentrations. We concluded that Exosurf and Survanta contain limited antioxidant activity compared with NLS.

Effect of the Molecular Structure on the Hierarchical Self-Assembly of Semifluorinated Alkanes at the Air/Water Interface

Langmuir ◽  
2011 ◽  
Vol 27 (14) ◽  
pp. 8776-8786 ◽  
Author(s):  
Laurence de Viguerie ◽  
Rabea Keller ◽  
Ulrich Jonas ◽  
Rüdiger Berger ◽  
Christopher G. Clark ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Self Assembly ◽  
Water Interface ◽  
Semifluorinated Alkanes ◽  
Air Water Interface

scholarly journals Life under Continuous Streaming: Recrystallization of Low Concentrations of Bacterial SbpA in Dynamic Flow Conditions

Coatings ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 76 ◽  
Author(s):  
Jagoba Iturri ◽  
Alberto Moreno-Cencerrado ◽  
José Toca-Herrera
Keyword(s):  
Self Assembly ◽  
Divalent Cations ◽  
Crystal Formation ◽  
Flow Conditions ◽  
Dynamic Flow ◽  
Protein Film ◽  
Force Microscopy ◽  
Low Concentrations ◽  
Physico Chemical ◽  
Protein Supply

The well-known bacterial S-layer protein SbpA from Lysinibacillus sphaericus CCM2177 induces spontaneous crystal formation via cooperative self-assembly of the protein subunits into an ordered supramolecular structure. Recrystallization occurs in the presence of divalent cations (i.e., Ca2+) and finally leads to producing smooth 2-D crystalline coatings composed of squared (p4) lattice structures. Among the factors interfering in such a process, the rate of protein supply certainly plays an important role since a limited number of accessible proteins might turn detrimental for film completion. Studies so far have mostly focused on high SbpA concentrations provided under stopped-flow or dynamic-flow conditions, thus omitting the possibility of investigating intermediate states, in which dynamic flow is applied for more critical concentrations of SbpA (i.e., 25, 10, and 5 µg/mL). In this work, we have characterized both physico-chemical and topographical aspects of the assembly and recrystallization of SbpA protein in such low concentration conditions by means of in situ Quartz Crystal Microbalance with Dissipation (QCMD) and atomic force microscopy (AFM) measurements, respectively. On the basis of these experiments, we can confirm how the application of a dynamic flow influences the formation of a closed and crystalline protein film from low protein concentrations (i.e., 10 µg/mL), which otherwise would not be formed.

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