Chakraborty Aishik, Hui Erica, Waring Alan J, Dhar Prajnaparamita
Department of Chemical Engineering, University of Kansas, KS 66045, United States.
Department of Medicine, Harbor UCLA Medical Center - LA BioMed, CA 90502, United States; Department of Physiology and Biophysics, University of California, Irvine, CA 92697, United States.
Biochim Biophys Acta. 2016 Apr;1858(4):904-12. doi: 10.1016/j.bbamem.2016.01.008. Epub 2016 Jan 15.
The overall goal of this work is to study the combined effects of Mini-B, a 34 residue synthetic analog of the lung surfactant protein SP-B, and cholesterol, a neutral lipid, on a model binary lipid mixture containing dipalmitolphosphatidylcholine (DPPC) and palmitoyl-oleoyl-phosphatidylglycerol (POPG), that is often used to mimic the primary phospholipid composition of lung surfactants. Using surface pressure vs. mean molecular area isotherms, fluorescence imaging and analysis of lipid domain size distributions; we report on changes in the structure, function and stability of the model lipid-protein films in the presence and absence of varying composition of cholesterol. Our results indicate that at low cholesterol concentrations, Mini-B can prevent cholesterol's tendency to lower the line tension between lipid domain boundaries, while maintaining Mini-B's ability to cause reversible collapse resulting in the formation of surface associated reservoirs. Our results also show that lowering the line tension between domains can adversely impact monolayer folding mechanisms. We propose that small amounts of cholesterol and synthetic protein Mini-B can together achieve the seemingly opposing requirements of efficient LS: fluid enough to flow at the air-water interface, while being rigid enough to oppose irreversible collapse at ultra-low surface tensions.
这项工作的总体目标是研究肺表面活性蛋白SP-B的34个残基合成类似物Mini-B和中性脂质胆固醇对含有二棕榈酰磷脂酰胆碱(DPPC)和棕榈酰油酰磷脂酰甘油(POPG)的模型二元脂质混合物的联合作用,该混合物常用于模拟肺表面活性剂的主要磷脂组成。通过表面压力与平均分子面积等温线、荧光成像以及脂质域大小分布分析;我们报告了在有无不同胆固醇组成情况下模型脂质-蛋白质膜结构、功能和稳定性的变化。我们的结果表明,在低胆固醇浓度下,Mini-B可以防止胆固醇降低脂质域边界间线张力的倾向,同时保持Mini-B引起可逆塌陷从而形成表面相关储库的能力。我们的结果还表明,降低域间线张力会对单层折叠机制产生不利影响。我们提出,少量胆固醇和合成蛋白Mini-B可以共同实现高效肺表面活性剂看似相互矛盾的要求:足够流体化以在气-水界面流动,同时足够刚性以抵抗超低表面张力下的不可逆塌陷。