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
复制标题
肺表面活性剂单层中的表面活性剂蛋白 SP-B 和 SP-C：由特定蛋白质-脂质相互作用控制的物理性质
DOI：
10.1101/2022.12.12.520108
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Liekkinen J
中科院分区：
文献类型：
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作者：
Liekkinen J
肺泡内壁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，能够在吸入的空气和循环之间进行有效的气体交换。尽管对肺表面活性剂的研究取得了数十年的进展，但表面活性剂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剂行为中的固有作用尚未完全理解。在这个复杂系统中最重要的蛋白质是表面活性剂蛋白SP-B和SP-C。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研究的SP-B和SP-C的相互作用与多组分脂质单分子层模仿肺表面活性剂的组合物。的模拟补充Z-扫描荧光相关光谱和原子力显微镜测量。我们的国家的最先进的模拟模型再现实验压力面积等温线和横向扩散系数。与以前的研究一致，包括SP-B和SP-C增加表面压力，我们的模拟提供了一个分子尺度的解释这种效果：蛋白质显示优先脂质与磷脂酰甘油的相互作用，它们主要驻留在脂质酰基链区域，它们分区到液体膨胀相，甚至诱导它在其他包装单层。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脂质和蛋白质在表面活性剂功能中的作用，从而有助于开发更好的表面活性剂替代疗法合成产品，用于治疗许多致命的肺相关损伤和疾病。
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 byz-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.