|Alternative Title||Adsorption of the pulmonary surfactant at interfaces and the associated bio logical effects|
|Place of Conferral||北京|
|Keyword||肺表面活性剂 磷脂 界面吸附 生物膜 生物分子冕 分子动力学模拟|
肺表面活性剂是由II 型肺泡细胞合成和分泌的脂质蛋白质复合物质，可以吸附在肺泡的表面，在界面处形成单层膜， 这一层膜能够将肺泡的表面张力降低到非常低 ，以维持正常的呼吸作用 。肺表面活性剂膜也是抵御吸入的纳米颗粒的第一道屏障。当纳米颗粒与肺表面活性剂膜接触时，它们可以吸附肺表面活性剂的磷脂脂和蛋白质，从而在其表面上形成称之为脂蛋白冕的结构 。该脂蛋白冕赋予了纳米颗粒新的生物识别身份，并影响纳米颗粒的生物效应。因此， 研究肺表面活性剂在表面或界面（包括空气水界面和纳米颗粒表面）上的吸附，对于研究肺表面活性剂的生物物理功能和生物效应至关重要。
Pulmonary surfactant is a lipid-protein complex that is synthesized and secreted by type II alveolar cells. It can adsorb at the surface of the alveolar fluid to form a pulmonary surfactant film at the interface, which can reduce the surface tension of the alveolar fluid to very low values to maintain the normal tidal breathe. The pulmonary surfactant film is also the first barrier that defences the inhaled nanoparticles. When the nanoparticles contact with the pulmonary surfactant film, they can adsorb the phospholipids and proteins of the pulmonary surfactant to form the so-called lipoprotein coronas on their surfaces. This corona defines the new identity of the nanoparticles and affect the bio-effect of the nanoparticles, such as their interactions with the alveolar cells. Therefore, study of the adsorption of the pulmonary surfactant at the surfaces or interfaces, including the air-water interface and the surface of the nanoparticles, is crucial for the biophysical functions and the bio-effect of the pulmonary surfactant.
Although there have been many existing experimental studies on the adsorption of the pulmonary surfactant at the interfaces or surfaces. It is still challenging to reveal the molecular structure of adsorbed pulmonary surfactant and the dynamic adsorption process. Using combined experiments with constrained drop surfactometry (CDS) and coarse-grained molecular dynamics simulations, here we first studied the biophysical mechanisms of the adsorption of the dipalmitoylphosphatidylcholine (DPPC), the main component of the pulmonary surfactant, at the air-water surface. It was found that the DPPC film adsorbed from vesicles showed distinct equilibrium surface tensions from the DPPC monolayer spread via organic solvents. Our simulations revealed that only the outer leaflet of the DPPC vesicle is capable of unzipping and spreading at the air-water surface, whereas the inner leaflet remains intact and forms an inverted micelle to the interfacial monolayer. This inverted micelle increases the local curvature of the monolayer, thus leading to a loosely packed monolayer at the air-water surface and hence a higher equilibrium surface tension.
Using the coarse-grained molecular dynamics simulations, we studied the adsorption of the multi-component pulmonary surfactant at the air-water interface. It was found that the adsorption of the phospholipids with larger head groups than DPPC can reach to a lower surface tension. The unsaturated lipid tails and cholesterols can also help reduce the surface tension of the adsorbed pulmonary surfactant to a much lower value by stabilizing the curvature of the adsorbed structure and enhancing the interactions between the tails of the inverted micelle. Through the experimental technology, including gradient centrifugation and high performance liquid chromatography-mass spectrometry, we quantificationally analyzed the phospholipid components of the adsorbed natural pulmonary surfactant on the nanoparticles. We found that the adsorption of the pulmonary surfactant was driven by the adhesion energy between the pulmonary surfactant film and the nanoparticles surface, which can be tuned by the modification of the nanoparticles and also the external forces. The additional analysis indicated that the component of the phospholipids of the corona was different from the original pulmonary component, which was possibly due to the attractions between the nanoparticles with the specific lipids and the bending modulus of the lipids.
Using the dissipative particle dynamics simulations, we studied the bio-effect of the adsorption of the pulmonary surfactant on the nanoparticles that was the interactions between the cell membrane and the nanoparticles coated with a pulmonary surfactant layer. We investigated how the physicochemical properties of the coating pulmonary surfactant lipids and proteins affected the membrane response for inhaled nanoparticles respectively. We pinpointed several key factors in endocytosis of lipid NPs, including the deformation of the coating lipids, coating lipids density and ligand-receptor binding strength. Further studies revealed that the deformation of the coating lipids consumed energy but on the other hand promotes the coating ligands to bind with receptors more tightly. The coating lipids density controls the amount of the ligands as well as the hydrophobicity of the lipid NP, thus affecting the endocytosis kinetics through the specific and non-specific interactions respectively. It was also found that the hydrophobic surfactant proteins associated with lipids can accelerate the endocytosis process of the NPs, but the endocytosis efficiency mainly depended on the density of the coating surfactant lipids.
|白轩. 肺表面活性剂的界面吸附及其生物效应研究[D]. 北京. 中国科学院大学,2019.|
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