Fluorinated Alcohols' Effects on Lipid Bilayer Properties.
Fluorinated Alcohols' Effects on Lipid Bilayer Properties.
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氟化醇对脂质双层特性的影响。
DOI：
10.1016/j.bpj.2018.07.010
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发表时间：
2018
影响因子：
3.4
通讯作者：
Ingólfsson,HelgiI
中科院分区：
文献类型：
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作者：
Zhang,Mike;Peyear,Thasin;Patmanidis,Ilias;Greathouse,DeniseV;Marrink,SiewertJ;Andersen,OlafS;Ingólfsson,HelgiI
氟化醇（氟代醇）具有使它们成为肽、蛋白质和其他化合物的优良溶剂的物理化学性质。与其他醇类一样，氟代醇类也会改变膜蛋白的功能和脂质双层的性质和稳定性。因此，问题出现了：氟代醇作为脂质双层干扰化合物的效力如何，加入溶解在氟代醇中的化合物后残留的少量残余物是否足以改变脂质双层的性质，从而影响膜和膜蛋白的功能，它们的行为是否与其他醇相似？为了解决这些问题，我们使用了短杆菌肽为基础的荧光测定，以确定选定的氟代醇：三氟乙醇（TFE），HFIP和全氟叔丁醇（PFTB）的双层修饰效力。这些氟代醇在低（PFTB）到高（TFE）mM范围内改变双层性质。使用相同的测定，我们确定了醇的双层分配。当涉及到水溶液的浓度，氟代醇是更多的双层扰动比他们的非氟化对应物，与最大的氟代醇，PFTB，是最有效的和最小的，TFE，最少。然而，当提及膜中的摩尔分数时，氟代醇具有与它们的非氟化对应物相等或更小的双层扰动效力，其中TFE比PFTB更双层扰动。我们用原子分子动力学模拟比较了氟代醇的分子水平双层相互作用，并用吸光度测量和31P核磁共振显示了在较高浓度下它们如何引起双层破裂。
Fluorinated alcohols (fluoroalcohols) have physicochemical properties that make them excellent solvents of peptides, proteins, and other compounds. Like other alcohols, fluoroalcohols also alter membrane protein function and lipid bilayer properties and stability. Thus, the questions arise: how potent are fluoroalcohols as lipid-bilayer-perturbing compounds, could small residual amounts that remain after adding compounds dissolved in fluoroalcohols alter lipid bilayer properties sufficiently to affect membranes and membrane protein function, and do they behave like other alcohols? To address these questions, we used a gramicidin-based fluorescence assay to determine the bilayer-modifying potency of selected fluoroalcohols: trifluoroethanol (TFE), HFIP, and perfluoro-tert-butanol (PFTB). These fluoroalcohols alter bilayer properties in the low (PFTB) to high (TFE) mM range. Using the same assay, we determined the bilayer partitioning of the alcohols. When referenced to the aqueous concentrations, the fluoroalcohols are more bilayer perturbing than their nonfluorinated counterparts, with the largest fluoroalcohol, PFTB, being the most potent and the smallest, TFE, the least. When referenced to the mole fractions in the membrane, however, the fluoroalcohols have equal or lesser bilayer-perturbing potency than their nonfluorinated counterparts, with TFE being more bilayer perturbing than PFTB. We compared the fluoroalcohols' molecular level bilayer interactions using atomistic molecular dynamics simulations and showed how, at higher concentrations, they can cause bilayer breakdown using absorbance measurements and31P nuclear magnetic resonance.