Department of Biochemistry and Molecular Biology, Faculty of Biology and Research Institute "Hospital 12 Octubre (imas12)", Complutense University, Madrid, Spain.
Arch Biochem Biophys. 2021 May 30;703:108850. doi: 10.1016/j.abb.2021.108850. Epub 2021 Mar 20.
Lung surfactant (LS) is an outstanding example of how a highly regulated and dynamic membrane-based system has evolved to sustain a wealth of structural reorganizations in order to accomplish its biophysical function, as it coats and stabilizes the respiratory air-liquid interface in the mammalian lung. The present review dissects the complexity of the structure-function relationships in LS through an updated description of the lipid-protein interactions and the membrane structures that sustain its synthesis, secretion, interfacial performance and recycling. We also revise the current models and the biophysical techniques employed to study the membranous architecture of LS. It is important to consider that the structure and functional properties of LS are often studied in bulk or under static conditions, in spite that surfactant function is strongly connected with a highly dynamic behaviour, sustained by very polymorphic structures and lipid-lipid, lipid-protein and protein-protein interactions that reorganize in precise spatio-temporal coordinates. We have tried to underline the evidences available of the existence of such structural dynamism in LS. A last important aspect is that the synthesis and assembly of LS is a strongly regulated intracellular process to ensure the establishment of the proper interactions driving LS surface activity, while protecting the integrity of other cell membranes. The use of simplified lipid models or partial natural materials purified from animal tissues could be too simplistic to understand the true molecular mechanisms defining surfactant function in vivo. In this line, we will bring into the attention of the reader the methodological challenges and the questions still open to understand the structure-function relationships of LS at its full biological relevance.
肺表面活性剂（LS）是一个极好的例子，说明了一个高度调节和动态的基于膜的系统是如何进化的，以维持大量的结构重组，从而完成其生物物理功能，因为它覆盖并稳定了哺乳动物肺中的呼吸气液界面。本综述通过更新描述脂质-蛋白相互作用和维持其合成、分泌、界面性能和再循环的膜结构，剖析了 LS 结构-功能关系的复杂性。我们还修正了目前用于研究 LS 膜状结构的模型和生物物理技术。重要的是要考虑到，尽管表面活性剂的功能与高度动态的行为密切相关，但其结构和功能特性通常在批量或静态条件下进行研究，这是由非常多态的结构以及脂质-脂质、脂质-蛋白和蛋白-蛋白相互作用维持的，这些相互作用在精确的时空坐标中重新排列。我们试图强调 LS 中存在这种结构动态性的现有证据。最后一个重要的方面是，LS 的合成和组装是一个强烈调节的细胞内过程，以确保建立适当的相互作用，从而驱动 LS 的表面活性，同时保护其他细胞膜的完整性。使用简化的脂质模型或从动物组织中纯化的部分天然材料可能过于简单，无法理解体内表面活性剂功能的真正分子机制。在这方面，我们将提请读者注意在充分了解 LS 的生物学相关性时，方法学上的挑战和仍然存在的问题。
