Depth Profiles of Pulmonary Surfactant Protein B in Phosphatidylcholine Bilayers, Studied by Fluorescence and Electron Spin Resonance Spectroscopy

Cruz, Antonio; Casals, Cristina; Plasencia, I; Marsh, Derek; Pérez‐Gil, Jesús

doi:10.1021/bi971558v

Cited by 58 publications

(62 citation statements)

References 44 publications

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“…SP-B, on the other hand, is less hydrophobic than SP-C and does not form transmembrane structures as SP-C does. It has been estimated that in the membrane and film of natural PS, SP-B likely interacts with the phospholipid molecules through the main axis of its amphipathic helical segments orientated in parallel to the plane of the lipid bilayers; 37 however, SP-C, being an even more hydrophobic protein, most likely assumes a transmembrane orientation. Our MD simulations suggest that each of these proteins in the PS corona may assume a molecular orientation similar to that in the PS membranes.…”

Section: Resultsmentioning

confidence: 99%

Unveiling the Molecular Structure of Pulmonary Surfactant Corona on Nanoparticles

et al. 2017

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The growing risk of human exposure to airborne nanoparticles (NPs) causes a general concern on the biosafety of nanotechnology. Inhaled NPs can deposit in the deep lung at which they interact with the pulmonary surfactant (PS). Despite the increasing study of nano-bio interactions, detailed molecular mechanisms by which inhaled NPs interact with the natural PS system remain unclear. Using coarse-grained molecular dynamics simulation, we studied the interaction between NPs and the PS system in the alveolar fluid. It was found that regardless of different physicochemical properties, upon contacting the PS, both silver and polystyrene NPs are immediately coated with a biomolecular corona that consists of both lipids and proteins. Structure and molecular conformation of the PS corona depend on the hydrophobicity of the pristine NPs. Quantitative analysis revealed that lipid composition of the corona formed on different NPs is relatively conserved and is similar to that of the bulk phase PS. However, relative abundance of the surfactant-associated proteins, SP-A, SP-B, and SP-C, is notably affected by the hydrophobicity of the NP. The PS corona provides the NPs with a physicochemical barrier against the environment, equalizes the hydrophobicity of the pristine NPs, and may enhance biorecognition of the NPs. These modifications in physicochemical properties may play a crucial role in affecting the biological identity of the NPs and hence alter their subsequent interactions with cells and other biological entities. Our results suggest that all studies of inhalation nanotoxicology or NP-based pulmonary drug delivery should consider the influence of the PS corona.

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Section: Resultsmentioning

confidence: 99%

Unveiling the Molecular Structure of Pulmonary Surfactant Corona on Nanoparticles

et al. 2017

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“…However, a molecular structure of SP-B, the only member of the saposin family that is permanently associated with membranes, is still not available despite the fact that some molecular modelling efforts have been reported [69,70]. Numerous studies have approached the analysis of structural determinants in SP-B by means of indirect techniques such as circular dichroism [71,72] [73], fluorescence [74] or infrared spectroscopies [75,76], or electron spin resonance (ESR) [77]. The protein structure is dominated by a 40-50% "-helix, predicted to be in the form of amphipathic helical segments with well-defined polar and non-polar faces.…”

Section: Structure-function Relationships Of Sp-bmentioning

confidence: 99%

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Mingarro¹,

Lukovic²,

Vilar³

et al. 2008

CMC

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

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“…Although previous studies have shown that solvent-spread SP-C/phospholipid monolayers are similar to monolayers adsorbed from bilayers (Nag et al 1996), this has not been demonstrated for SP-B-containing systems. In determining potential equivalence for SP-B-containing ®lms formed by spreading versus adsorption, one must consider that the nature of the interaction of SP-B with phospholipid bilayers and its consequent surface activity is dependent on the method used to reconstitute lipid-protein samples (Cruz et al , 1998.…”

Section: Introductionmentioning

confidence: 99%

Microstructure and dynamic surface properties of surfactant protein SP-B/dipalmitoylphosphatidylcholine interfacial films spread from lipid-protein bilayers

Cruz¹,

Worthman

Serrano³

et al. 2000

Eur Biophys J

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Suspensions of dipalmitoylphosphatidylcholine (DPPC) bilayers containing 5, 10 or 20% (w/w) surfactant protein SP-B have been reconstituted and spread at air-liquid interfaces. Compression isotherms of DPPC/SP-B monolayers spread from these preparations were qualitatively comparable to the isotherms of the corresponding DPPC/SP-B monolayers spread from solvents. SP-B was squeezed-out at higher pressures from vesicle-spread films than from solvent-spread monolayers. SP-B caused a marked decrease on the rate of relaxation of DPPC collapse phases to equilibrium pressures in all the lipid/protein films assayed. This stabilizing effect was higher in vesicle-spread than in solvent-spread monolayers. Inclusion in the films of traces of the fluorescent probe NBD-PC (1 mol%) and use of a fluorescent derivative of SP-B labeled with a rhodamine derivative, Texas Red, allowed for direct observation of protein and lipid domains at the interface by epifluorescence microscopy. Upon compression, SP-B altered the packing of phospholipids in the bilayer-spread films, observed as a SP-B-induced reduction of the area of liquid-condensed domains, in a way similar to its effect in solvent-spread monolayers. SP-B was not associated with condensed regions of the films. Fluorescence images from vesicle-spread films showed discrete fluorescent aggregates that could be consistent with the existence of lipid-protein vesicles in close association with the monolayer. Both the retention of SP-B at higher surface pressures and the greater stability of collapse phases of DPPC/SP-B films prepared by spreading from liposomes in comparison to those spread from solvents can be interpreted as a consequence of formation of complex bilayer-monolayer interacting systems.

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Depth Profiles of Pulmonary Surfactant Protein B in Phosphatidylcholine Bilayers, Studied by Fluorescence and Electron Spin Resonance Spectroscopy

Cited by 58 publications

References 44 publications

Unveiling the Molecular Structure of Pulmonary Surfactant Corona on Nanoparticles

Unveiling the Molecular Structure of Pulmonary Surfactant Corona on Nanoparticles

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Microstructure and dynamic surface properties of surfactant protein SP-B/dipalmitoylphosphatidylcholine interfacial films spread from lipid-protein bilayers

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