Laing Cameron, Baoukina Svetlana, Tieleman D Peter
Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary AB, Canada T2N 1N4.
Phys Chem Chem Phys. 2009 Mar 28;11(12):1916-22. doi: 10.1039/b819767a. Epub 2009 Feb 18.
We have investigated the effect of cholesterol concentration on the properties of lipid monolayers at air/water interfaces at low surface tensions. This is of interest for understanding the properties and function of lung surfactant monolayers. Lung surfactant lines the gas exchange interface in the lungs and dramatically reduces the surface tension, thereby preventing lung collapse and decreasing the work associated with breathing. Changes in the lipid composition of lung surfactant, particularly an increase in cholesterol concentration, can result in inhibition of its function, as in the case of acute respiratory distress syndrome. We have used molecular dynamics simulations with both atomistic and coarse-grained force fields to study lipid monolayers containing DPPC, POPG and cholesterol in molecular ratios of 8:2:1 and 4:1:4 at surface tensions of 40, 20 and 0 mN m(-1) at 310 K. These mixtures model the lipid component of lung surfactant at normal (approximately 9%) and elevated (approximately 44%) cholesterol concentration. We have characterised the structural and dynamic properties of these monolayers and calculated the free energy for transfer of each lipid from its equilibrium position in the monolayer into water and into air (vacuum). The results show that at low surface tensions an increase in cholesterol concentrations leads to formation of a liquid-condensed phase with low area compressibility, which is in agreement with experimental findings.
我们研究了胆固醇浓度对低表面张力下空气/水界面脂质单分子层性质的影响。这对于理解肺表面活性物质单分子层的性质和功能具有重要意义。肺表面活性物质覆盖在肺部的气体交换界面，可显著降低表面张力，从而防止肺塌陷并减少与呼吸相关的功。肺表面活性物质脂质组成的变化，尤其是胆固醇浓度的增加，可能导致其功能受到抑制，如在急性呼吸窘迫综合征中所见。我们使用了具有原子力场和粗粒化力场的分子动力学模拟，来研究在310 K下表面张力为40、20和0 mN m⁻¹时，含有DPPC、POPG和胆固醇且分子比例为8:2:1和4:1:4的脂质单分子层。这些混合物模拟了正常（约9%）和升高（约44%）胆固醇浓度下肺表面活性物质的脂质成分。我们对这些单分子层的结构和动力学性质进行了表征，并计算了每种脂质从其在单分子层中的平衡位置转移到水中和转移到空气中（真空）的自由能。结果表明，在低表面张力下，胆固醇浓度的增加会导致形成具有低面积压缩性的液态凝聚相，这与实验结果一致。
