The biophysical properties and biological functions of membranes are highly dependent on lipid composition. Supplementing cellular membranes with very long chain fatty acids (vlcFAs) is notoriously difficult given the extreme insolubility of vlcFAs in aqueous solution. Herein, we report a solvent-free, photochemical approach to enrich target membranes with vlcFA. To prevent aggregation of vlcFA, we created light-sensitive micelles composed exclusively of poly-ethylene-glycol-nervonic acid amphiphiles (NA-PEG), which spontaneously disassemble in the presence of lipid bilayers. Once embedded within a membrane, UV light is used to cleave off PEG, leaving free nervonic acid (NA, i.e. FA24:1) in the target membrane. When applied to living cells, free NA was processed by the cell to generate various species of membrane and other lipids with incorporated vlcFAs. In this way, we were able to alter the membrane lipid composition of cellular membranes and modulate the enzymatic activity of γ-secretase, an intramembrane protease whose dysfunction has been implicated in the onset and progression of Alzheimer's disease.

中文翻译：

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光控制非常长链脂肪酸向细胞膜的传递和膜蛋白功能的调节。

膜的生物物理特性和生物功能高度依赖脂质组成。众所周知，鉴于vlcFAs在水溶液中的极端不溶性，很难用长链脂肪酸（vlcFAs）补充细胞膜。在此，我们报告了一种无溶剂的光化学方法，可通过vlcFA富集目标膜。为了防止vlcFA聚集，我们创建了仅由聚乙二醇-神经氨酸两亲物（NA-PEG）组成的光敏胶束，该胶束在脂质双层的存在下自发分解。一旦包埋在膜中，便使用紫外线将PEG裂解，从而在目标膜中留下游离神经酸（NA，即FA24：1）。当应用于活细胞时，细胞处理游离的NA，生成各种种类的膜和其他脂质，并结合了vlcFA。通过这种方式，我们能够改变细胞膜的膜脂质组成并调节γ-分泌酶的酶活性，γ-分泌酶是一种功能障碍与阿尔茨海默氏病的发作和发展有关的膜内蛋白酶。