Interactions of drugs and amphiphiles with membranes: modulation of lipid bilayer elastic properties by changes in acyl chain unsaturation and protonation.
Interactions of drugs and amphiphiles with membranes: modulation of lipid bilayer elastic properties by changes in acyl chain unsaturation and protonation.
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DOI：
10.1039/c2fd20092a
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发表时间：
2013
影响因子：
3.4
通讯作者：
Andersen OS
中科院分区：
文献类型：
--
作者：
Bruno MJ;Rusinova R;Gleason NJ;Koeppe RE 2nd;Andersen OS
多不饱和脂肪酸（PUFA）改变许多膜蛋白的功能，而单不饱和脂肪酸通常是惰性的。我们先前表明，二十二碳六烯酸（DHA）在pH 7下降低双层刚度，这与两亲物诱导的弹性增加一致，但不与曲率的负变化一致;油酸（OA）是惰性的（Bruno，Koeppe和Andersen，Proc. Natl. Acad. Sci. USA 104：9638-9643）。为了进一步探索PUFA和其他两亲物如何改变脂质双层特性，从而改变膜蛋白的功能，我们研究了酰基链不饱和度的变化，以及头基电荷和大小，改变双层特性，如不同长度的跨双层短杆菌肽A（gA）通道所感知的。与DHA相比，中性DHA-甲酯对双层性质的影响降低，并且1-棕榈酰-2-二十二碳六烯酰-磷脂酰胆碱（PDPC）形成比二油酰磷脂酰胆碱（DOPC）更软的双层。通道功能的变化是较大的短gA通道，表明弹性的变化占主导地位的曲率变化。我们通过滴定改变了脂肪酸质子化：二十二碳六烯酸（DHA）在pH 9（相对于pH 7）下更有效，在pH 4下呈惰性; OA在pH 7下呈惰性，在pH 9下成为双层性质的有效改性剂。在pH 7和9，DHA和OA产生较大的变化，在短的gA通道的寿命，表明它们增加脂质双层弹性时，去质子化，虽然OA促进形成的倒六角形相在pH 7。带正电荷的油胺（OAM），它有一个小的头部基团，因此应该是一个负曲率的启动子，抑制gA通道功能，具有类似的减少寿命的短和长的gA通道，表明曲率主导的效果。监测的单通道电导，我们发现，带负电荷的脂肪酸增加的电导，通过增加通道周围的局部负电荷，而带正电荷的OAM没有影响。这些结果表明，去质子化的脂肪酸通过可逆地吸附在双层/溶液界面增加双层弹性。
Poly-unsaturated fatty acids (PUFAs) alter the function of many membrane proteins, whereas monounsatured fatty acids generally are inert. We previously showed that docosahexaenoic acid (DHA) at pH 7 decreases the bilayer stiffness, consistent with an amphiphile-induced increase in elasticity, but not with a negative change in curvature; oleic acid (OA) was inert (Bruno, Koeppe and Andersen, Proc. Natl. Acad. Sci. USA 104:9638–9643,). To further explore how PUFAs and other amphiphiles may alter lipid bilayer properties, and thus membrane protein function, we examined how changes in acyl chain unsaturation, and head group charge and size, alter bilayer properties, as sensed by bilayer-spanning gramicidin A (gA) channels of different lengths. Compared to DHA, the neutral DHA-methyl ester has reduced effects on bilayer properties, and 1-palmitoyl-2-docosahexaenoyl-phosphatidylcholine (PDPC) forms bilayers that are softer than dioleoylphosphatidylcholine (DOPC). The changes in channel function are larger for the short gA channels, indicating that changes in elasticity dominate over changes in curvature. We altered the fatty acid protonation by titration: docosahexaenoic acid (DHA) is more potent at pH 9 (relative to pH 7) and is inert at pH 4; OA, which was inert at pH 7, becomes a potent modifier of bilayer properties at pH 9. At both pH 7 and 9, DHA and OA produced larger changes in the lifetimes of the short gA channels, demonstrating that they increase lipid bilayer elasticity when deprotonated—though OA promotes the formation of inverted hexagonal phases at pH 7. The positively charged oleylamine (OAm), which has a small head-group and therefore should be a negative curvature promoter, inhibited gA channel function, with similar reductions in the lifetimes of the short and long gA channels, indicating a curvature-dominated effect. Monitoring the single-channel conductance, we find that the negatively charged fatty acids increase the conductance by increasing the local negative charge around the channel, whereas the positively charged OAm has no effect. These results suggest that deprotonated fatty acids increase bilayer elasticity by reversibly adsorbing at the bilayer/solution interface.
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影响因子：
3.6
作者：
Artigas, Pablo;Al'Aref, Subhi J.;Andersen, Olaf S.
通讯作者：
Andersen, Olaf S.
DOI：
10.1051/jphys:019900051010094500
发表时间：
1990-05-15
期刊：
JOURNAL DE PHYSIQUE
影响因子：
--
作者：
DUWE, HP;KAES, J;SACKMANN, E
通讯作者：
SACKMANN, E
影响因子：
15
作者：
Allen, TW;Andersen, OS;Roux, B
通讯作者：
Roux, B
DOI：
10.1084/jem.70.1.11
发表时间：
1939-06-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dubos RJ
通讯作者：
Dubos RJ
影响因子：
15
作者：
Huber, T;Rajamoorthi, K;Brown, MF
通讯作者：
Brown, MF