The Impact of Nonequilibrium Conditions in Lung Surfactant: Structure and Composition Gradients in Multilamellar Films,ACS Central Science

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The Impact of Nonequilibrium Conditions in Lung Surfactant: Structure and Composition Gradients in Multilamellar Films
ACS Central Science ( IF 12.7 ) Pub Date : 2018-09-24 00:00:00 , DOI: 10.1021/acscentsci.8b00362
Jenny Marie Andersson _{1,

2} , Kevin Roger ₂ , Marcus Larsson ₃ , Emma Sparr ₁

Affiliation

The lipid–protein mixture that covers the lung alveoli, lung surfactant, ensures mechanical robustness and controls gas transport during breathing. Lung surfactant is located at an interface between water-rich tissue and humid, but not fully saturated, air. The resulting humidity difference places the lung surfactant film out of thermodynamic equilibrium, which triggers the buildup of a water gradient. Here, we present a millifluidic method to assemble multilamellar interfacial films from vesicular dispersions of a clinical lung surfactant extract used in replacement therapy. Using small-angle X-ray scattering, infrared, Raman, and optical microscopies, we show that the interfacial film consists of several coexisting lamellar phases displaying a substantial variation in water swelling. This complex phase behavior contrasts to observations made under equilibrium conditions. We demonstrate that this disparity stems from additional lipid and protein gradients originating from differences in their transport properties. Supplementing the extract with cholesterol, to levels similar to the endogenous lung surfactant, dispels this complexity. We observed a homogeneous multilayer structure consisting of a single lamellar phase exhibiting negligible variations in swelling in the water gradient. Our results demonstrate the necessity of considering nonequilibrium thermodynamic conditions to study the structure of lung surfactant multilayer films, which is not accessible in bulk or monolayer studies. Our reconstitution methodology also opens avenues for lung surfactant pharmaceuticals and the understanding of composition, structure, and property relationships at biological air–liquid interfaces.

中文翻译：

肺表面活性剂非平衡条件的影响：多层膜的结构和组成梯度

覆盖肺泡，肺表面活性剂的脂质-蛋白质混合物可确保机械强度，并控制呼吸过程中的气体运输。肺表面活性剂位于富含水的组织和潮湿但未完全饱和的空气之间的界面。所产生的湿度差使肺表面活性剂薄膜脱离热力学平衡，从而触发水梯度的积累。在这里，我们提出了一种微流控方法，用于从替代治疗中使用的临床肺表面活性剂提取物的囊状分散体组装多层界面膜。使用小角度X射线散射，红外，拉曼光谱和光学显微镜，我们发现界面膜由几种共存的层状相组成，这些相在水溶胀方面表现出很大的差异。这种复杂的相行为与在平衡条件下进行的观察形成对比。我们证明了这种差异源于其他脂质和蛋白质梯度，这些脂质和蛋白质梯度源于其运输特性的差异。在提取物中添加胆固醇，使其水平类似于内源性肺表面活性剂，从而消除了这种复杂性。我们观察到由单个层状相组成的均质多层结构，在水梯度中溶胀变化可忽略不计。我们的结果表明需要考虑非平衡热力学条件来研究肺表面活性剂多层膜的结构，这在批量或单层研究中是无法获得的。我们的重组方法还为肺表面活性剂药物以及对成分，结构，

更新日期：2018-09-24

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