Low levels of lipid oxidation radically increase the passive permeability of lipid bilayers.
Low levels of lipid oxidation radically increase the passive permeability of lipid bilayers.
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DOI：
10.1039/c4sm01478b
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发表时间：
2015-01-21
期刊：
影响因子：
3.4
通讯作者：
Malmstadt N
中科院分区：
文献类型：
--
作者：
Runas KA;Malmstadt N
细胞膜中不饱和脂质的氧化已被证明会导致严重的膜损伤和潜在的细胞死亡。已知膜中氧化脂质物质的存在会引起膜性质的变化，例如流动性降低。本研究使用巨大的单层囊泡（GUV）来测量跨膜的被动转运，该膜含有确定浓度的氧化脂质物质。使用由饱和磷脂、不饱和磷脂和胆固醇组成的GUV作为模型膜。通过用相应的氧化产物替换限定量的不饱和脂质，可以模拟氧化过程，产生不同氧化脂质浓度的囊泡。氧化脂质浓度从总脂质浓度的0摩尔%至18摩尔%变化。使用微流体阱捕获GUV和旋转圆盘共聚焦显微镜（SDCM）跟踪荧光物质在每个GUV的赤道平面中的运输来测量PEG 12-NBD（一种不带电荷的荧光分子）的被动运输。通过将所得浓度曲线拟合至膜周围和通过膜的扩散和渗透的有限差分模型来确定膜渗透性。实验表明，三个渗透率制度。在没有氧化的情况下，传输是缓慢的，测得的渗透率约为1.5×10−6 cm/s。在2.5-10%的氧化物质渗透速度很快（1.5×10−5 cm/s）。高于12.5%的氧化物种，双层被破坏的孔缺陷的形成。由于被动转运是药物传递的一个重要机制，了解氧化和渗透之间的关系可以提供洞察与氧化损伤的组织的药物特性。
Oxidation of unsaturated lipids in cellular membranes has been shown to cause severe membrane damage and potentially cell death. The presence of oxidized lipid species in the membrane is known to cause changes in membrane properties, such as decreased fluidity. This study uses giant unilamellar vesicles (GUVs) to measure passive transport across membranes containing defined concentrations of oxidized lipid species. GUVs consisting of a saturated phospholipid, an unsaturated phospholipid, and cholesterol were used as model membranes. By replacing defined amounts of the unsaturated lipid with a corresponding oxidized product, the oxidation process could be mimicked, yielding vesicles of varying oxidized lipid concentration. Oxidized lipid concentration was varied from 0 mol% to 18 mol% of the total lipid concentration. Passive transport of PEG12-NBD, an uncharged fluorescent molecule, was measured using a microfluidic trap to capture the GUVs and spinning disk confocal microscopy (SDCM) to track the transport of a fluorescent species in the equatorial plane of each GUV. Membrane permeability was determined by fitting the resulting concentration profiles to a finite difference model of diffusion and permeation around and through the membrane. Experiments showed three permeability regimes. Without oxidation, transport was slow, with a measured permeability on the order of 1.5×10−6 cm/s. At 2.5–10% oxidized species permeation was fast (1.5×10−5 cm/s). Above 12.5% oxidized species, the bilayer was disrupted by the formation of pore defects. As passive transport is an important mechanism for drug delivery, understanding the relationship between oxidation and permeation could provide insight into the pharmaceutical characteristics of tissues with oxidative damage.
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DOI：
10.1016/s1388-1981(00)00084-6
发表时间：
2000-08-24
影响因子：
4.8
作者：
Borst, JW;Visser, NV;Visser, AJWG
通讯作者：
Visser, AJWG
影响因子：
3.4
作者：
Sabatini, Karen;Mattila, Juha-Pekka;Kinnunen, Paavo K. J.
通讯作者：
Kinnunen, Paavo K. J.
影响因子：
3.4
作者：
Sankhagowit, Shalene;Wu, Shao-Hua;Malmstadt, Noah
通讯作者：
Malmstadt, Noah
影响因子：
3.4
作者：
Mertins, Omar;Bacellar, Isabel O. L.;Itri, Rosangela
通讯作者：
Itri, Rosangela
影响因子：
7.4
作者：
Cadenas, E;Davies, KJA
通讯作者：
Davies, KJA