Permeability of membranes in the liquid ordered and liquid disordered phases

Permeability of membranes in the liquid ordered and liquid disordered phases
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DOI:
10.1038/s41467-019-13432-7
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发表时间:
2019-12-09
影响因子:
16.6
通讯作者:
Pastor, Richard W.
Pastor, Richard W.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ghysels, An;Kramer, Andreas;Pastor, Richard W.

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富含胆固醇的真核细胞膜中有序的纳米结构域(或木筏)的功能意义才刚刚开始探索。本研究利用三组分脂双层的胞筏和液体有序(L-o)相的对应关系来检测通透性。L-O相二棕榈酰磷脂酰胆碱、二油酰磷脂酰胆碱和胆固醇的分子动力学模拟表明,氧气和水通过六方堆积的二棕榈酰磷脂酰胆碱微区的DOPC和胆固醇的富含边界,沿双层中面自由扩散,并沿边界区域逃逸。电子顺磁共振实验提供了关键的验证:测得的无序液体(L-d)和L-o双层膜的氧浓度比为1.75+/-0.35,与模拟得到的1.3+/-0.3非常一致。结果表明,细胞筏可以是结构上刚性的信号平台,同时保持几乎像L-d相一样对小分子的渗透性。
The functional significance of ordered nanodomains (or rafts) in cholesterol rich eukaryotic cell membranes has only begun to be explored. This study exploits the correspondence of cellular rafts and liquid ordered (L-o) phases of three-component lipid bilayers to examine permeability. Molecular dynamics simulations of L-o phase dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), and cholesterol show that oxygen and water transit a leaflet through the DOPC and cholesterol rich boundaries of hexagonally packed DPPC microdomains, freely diffuse along the bilayer midplane, and escape the membrane along the boundary regions. Electron paramagnetic resonance experiments provide critical validation: the measured ratio of oxygen concentrations near the midplanes of liquid disordered (L-d) and L-o bilayers of DPPC/DOPC/cholesterol is 1.75 +/- 0.35, in very good agreement with 1.3 +/- 0.3 obtained from simulation. The results show how cellular rafts can be structurally rigid signaling platforms while remaining nearly as permeable to small molecules as the L-d phase.