Surfactant Proteins SP-B and SP-C in Pulmonary Surfactant Monolayers: Physical Properties Controlled by Specific Protein-Lipid Interactions.
Surfactant Proteins SP-B and SP-C in Pulmonary Surfactant Monolayers: Physical Properties Controlled by Specific Protein-Lipid Interactions.
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DOI：
10.1021/acs.langmuir.2c03349
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发表时间：
2023-03-28
期刊：
影响因子：
3.9
通讯作者：
Vattulainen, Ilpo
中科院分区：
文献类型：
--
作者：
Liekkinen, Juho;Olzynska, Agnieszka;Cwiklik, Lukasz;de la Serna, Jorge Bernardino;Javanainen, Matti;Vattulainen, Ilpo
肺泡的内层覆盖着肺表面活性物质，这是一种表面活性脂质和蛋白质的复杂混合物，使吸入的空气和循环之间能够进行有效的气体交换。尽管肺表面活性物质的研究已经取得了几十年的进展，但对表面活性物质的分子尺度行为以及不同脂质和蛋白质的数量在表面活性物质行为中的内在作用尚不完全清楚。在这个复杂的体系中最重要的蛋白质是表面活性蛋白SP-B和SP-C。有鉴于此，在这项工作中，我们进行了非平衡全原子分子动力学模拟，以研究SP-B和SP-C与多组分脂质单层在组成上模拟肺表面活性物质的相互作用。模拟得到了z扫描荧光相关光谱和原子力显微镜测量的补充。我们最先进的模拟模型再现了实验中的压力-面积等温线和横向扩散系数。与以前的研究一致，SP-B和SP-C的加入增加了表面压力，我们的模拟为这种效应提供了分子尺度的解释：蛋白质显示出优先与磷脂酰甘油的脂类相互作用，它们主要位于脂酰链区域，它们分配到液体扩展相，甚至在其他填充的单层中诱导它。后一种效应在我们的原子力显微镜图像中也是可见的。这项研究有助于更好地了解特定的脂质和蛋白质在表面活性物质功能中的作用，从而有助于开发更好的合成产品，用于表面活性物质替代疗法，用于治疗许多与肺相关的致命损伤和疾病。
The lining of the alveoli is covered by pulmonary surfactant, a complex mixture of surface-active lipids and proteins that enables efficient gas exchange between inhaled air and the circulation. Despite decades of advancements in the study of the pulmonary surfactant, the molecular scale behavior of the surfactant and the inherent role of the number of different lipids and proteins in surfactant behavior are not fully understood. The most important proteins in this complex system are the surfactant proteins SP-B and SP-C. Given this, in this work we performed nonequilibrium all-atom molecular dynamics simulations to study the interplay of SP-B and SP-C with multicomponent lipid monolayers mimicking the pulmonary surfactant in composition. The simulations were complemented by z-scan fluorescence correlation spectroscopy and atomic force microscopy measurements. Our state-of-the-art simulation model reproduces experimental pressure–area isotherms and lateral diffusion coefficients. In agreement with previous research, the inclusion of either SP-B and SP-C increases surface pressure, and our simulations provide a molecular scale explanation for this effect: The proteins display preferential lipid interactions with phosphatidylglycerol, they reside predominantly in the lipid acyl chain region, and they partition into the liquid expanded phase or even induce it in an otherwise packed monolayer. The latter effect is also visible in our atomic force microscopy images. The research done contributes to a better understanding of the roles of specific lipids and proteins in surfactant function, thus helping to develop better synthetic products for surfactant replacement therapy used in the treatment of many fatal lung-related injuries and diseases.
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