An elevated level of cholesterol impairs self-assembly of pulmonary surfactant into a functional film

被引:84
作者
Leonenko, Zoya
Gill, Simardeep
Baoukina, Svetlana
Monticelli, Luca
Doehner, Jana
Gunasekara, Lasantha
Felderer, Florian
Rodenstein, Mathias
Eng, Lukas M.
Amrein, Matthias [1 ]
机构
[1] Univ Calgary, Fac Med, Dept Cell Biol & Anat, Calgary, AB T2N 1N4, Canada
[2] Univ Calgary, Fac Sci, Dept Biol Sci, Calgary, AB T2N 1N4, Canada
[3] Tech Univ Dresden, Inst Appl Photophys, Dresden, Germany
基金
加拿大健康研究院; 加拿大创新基金会;
关键词
D O I
10.1529/biophysj.107.106310
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
In adult respiratory distress syndrome, the primary function of pulmonary surfactant to strongly reduce the surface tension of the air-alveolar interface is impaired, resulting in diminished lung compliance, a decreased lung volume, and severe hypoxemia. Dysfunction coincides with an increased level of cholesterol in surfactant which on its own or together with other factors causes surfactant failure. In the current study, we investigated by atomic force microscopy and Kelvin-probe force microscopy how the increased level of cholesterol disrupts the assembly of an efficient. lm. Functional surfactant films underwent a monolayer-bilayer conversion upon contraction and resulted in a. lm with lipid bilayer stacks, scattered over a lipid monolayer. Large stacks were at positive electrical potential, small stacks at negative potential with respect to the surrounding monolayer areas. Dysfunctional films formed only few stacks. The surface potential of the occasional stacks was also not different from the surrounding monolayer. Based on. lm topology and potential distribution, we propose a mechanism for formation of stacked bilayer patches whereby the helical surfactant-associated protein SP-C becomes inserted into the bilayers with defined polarity. We discuss the functional role of the stacks as mechanically reinforcing elements and how an elevated level of cholesterol inhibits the formation of the stacks. This offers a simple biophysical explanation for surfactant inhibition in adult respiratory distress syndrome and possible targets for treatment.
引用
收藏
页码:674 / 683
页数:10
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