Cholesterol's aliphatic side chain modulates membrane properties.
Cholesterol's aliphatic side chain modulates membrane properties.
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DOI：
10.1002/anie.201306753
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发表时间：
2013-12-02
影响因子：
16.6
通讯作者：
Huster, Daniel
中科院分区：
文献类型：
--
作者：
Scheidt, Holger A.;Meyer, Thomas;Nikolaus, Joerg;Baek, Dong Jae;Haralampiev, Ivan;Thomas, Lars;Bittman, Robert;Mueller, Peter;Herrmann, Andreas;Huster, Daniel
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The composition and chemical structures of the membrane forming molecules determine all essential properties of nature’s most important interface. Cellular membranes are subject to a hierarchical domain organization on the mesoscopic length scale.[1] This is triggered by preferential interactions between the major constituents of the membrane, eg phospholipids, cholesterol (Chol), glycolipids, and membrane proteins.[2] In particular, the attractive interactions between Chol and sphingolipids or saturated phospholipids and/or membrane proteins have been identified as the driving force for membrane domain formation.[3] Key to the lipid phase separation phenomena is the preferential interaction of Chol with saturated lipid chains.[4] Numerous examples of the specific interaction between Chol and saturated phospholipids or sphingomyelin have been reported.[5] The interaction between Chol and saturated lipid chains is thought to originate by attractive van der Waals interactions between Chol’s planar and rigid ring system (particularly the smooth α-face) and the saturated phospholipid chains.[6] This leads to a stiffening of the lipid chains, as indicated by an order increase, which is referred to as area condensation.[7] This increased packing density decreases membrane permeability.[8] Surprisingly, the influence of the aliphatic Chol side chain on lipid condensation and membrane domain formation is still not fully understood. Therefore, we have systematically studied the influence of the methylbranched (iso-series) side chain of Chol with 5 to 14 carbon atoms [9](Figure 1A) on important membrane properties.To evaluate the influence of the Chol side chain on the area condensation effect, 2H NMR order parameters [4] were measured for mixtures of either fully saturated DPPC-d62 or monounsaturated POPC-d31 with 20 mol% of the respective sterol analog (2H NMR spectra and order parameter plots are shown in supplementary Figures S1–S4). Pure lipid membranes are used as a reference featuring lowest chain order. Saturated DPPC shows higher order parameters than the monounsaturated POPC. All sterols studied induce an increase in lipid chain order, ie condensation but the degree of condensation varies as a function of the length of the iso-branched side chain. These differences are best displayed in the plot of the average order parameters< S> of the phospholipid in the presence of the sterols with varying length of the side chain (Figure 1B). There is a gradual increase in the POPC chain order from androst-5-en-3-β-ol (androstenol), which lacks a side chain, to i-C5-sterol, native Chol, and i-C10-sterol, while the longer chain i-C12-and i-C14-sterol analogs show decreasing condensation again. Most interestingly is the fact that the sterol ring system of Chol is only responsible for~ 40% of the lipid condensation as demonstrated for androstenol, while the i-C8 side chain of Chol accounts for~ 60% of the condensation. Furthermore, it is remarkable that native Chol induces a slightly lower lipid condensation than i-C10-sterol; for the latter, the lipid condensation is 6% higher.
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单个活细胞中生物传感器肽磷酸化的荧光寿命成像。
影响因子：
16.6
作者：
Damayanti, Nur P.;Parker, Laurie L.;Irudayaraj, Joseph M. K.
通讯作者：
Irudayaraj, Joseph M. K.
影响因子：
3.4
作者：
Baek, Dong Jae;Bittman, Robert
通讯作者：
Bittman, Robert
影响因子：
3.4
作者：
Huster, D;Jin, AJ;Gawrisch, K
通讯作者：
Gawrisch, K
影响因子：
1.9
作者：
HUANG, CH
通讯作者：
HUANG, CH
影响因子：
3.4
作者：
Frazier, Monica L;Wright, Jenny R;Pokorny, Antje;Almeida, Paulo F F
通讯作者：
Almeida, Paulo F F