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Transport of Endocrine Disruptors in Phospholipid Bilayer Membranes

磷脂双层膜中内分泌干扰物的转运

基本信息

批准号：
14540531
负责人：
OKAMURA Emiko
金额：
$ 1.79万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14540531/
关键词：
phospholipid bilayer endocrine disruptor membrane transport NMR diffusion bisphenol A octylphenol

项目摘要

Transport process of endocrine disruptors (ED) solubilized in phospholipid bilayer membranes was analyzed for the first time by NMR. The self-diffusion rates of ED, bisphenol A (BPA) and 4-octylphenol (OP), were directly determined and compared with those in water. Dynamics of the lipid matrices in membranes was simultaneously monitored without labeled nuclei. It owes its success to a specially designed high-power, high-sensitivity probe. The new probe can apply a large magnetic field-gradient sufficiently enough to monitor dynamic events in highly-viscous lipid membranes. Combining this probe to a high-resolution 600 MHz NMR apparatus, we showed how fast BPA, OP, and lipids moved in membrane and how the ED mobility was related to the membrane lipid dynamics. Attention was also paid to the relation of the ED mobility to the location in membrane.The ED transport in membrane was not rapid but more than one order of magnitude as slow as that in solution. ED had a high affinity for the membrane interface between the lipid headgroup and the hydrophobic core. The ED motion was slowed down by the site-specific, strong binding to membrane lipids and synchronized with that of the membrane lipid matrices.The slowdown of ED and lipid motions was leveled off in sufficiently large lipid bilayer vesicles, although the hydrodynamic continuum model gives the lipid aggregate motion slowed inversely to the spherical size. The limited motion is related to the intra-aggregate fluidity of the lipid bilayer membrane, the membrane not rigid but soft, fluctuating confined geometries. The method opens the possibility to give insight into the wide range of molecular dynamics within such confined but fluid intact cell membranes; neither labeling nor the invasive probing is required.

首次用核磁共振技术研究了内分泌干扰物(ED)在磷脂双层膜中的转运过程。直接测定了ED双酚A(BPA)和4-辛基苯酚(OP)的自扩散速率，并与水中的自扩散速率进行了比较。在没有标记核的情况下，同时监测了膜中脂基质的动力学。它的成功要归功于一种专门设计的高功率、高灵敏度的探头。新的探头可以施加足够大的磁场梯度来监测高粘性脂膜中的动态事件。将该探针与高分辨率600 MHz核磁共振仪器相结合，我们展示了BPA、OP和脂类在膜中移动的速度以及ED迁移率与膜脂动力学的关系。膜中ED的迁移速度不是很快，但比溶液慢一个数量级以上。ED对脂头基团和疏水核之间的膜界面具有很高的亲和力。在足够大的脂质双层囊泡中，ED和脂质运动的减慢是平稳的，尽管流体力学连续介质模型给出了与球形大小成反比的脂质聚集体运动。有限的运动与脂质双层膜的聚集内流动性有关，膜不是刚性的，而是柔软的，波动的受限几何形状。这种方法使我们有可能深入了解这种受限但流体完整的细胞膜中广泛的分子动力学；既不需要标记，也不需要侵入性探测。