Abstract:
A wide range of biomaterials and engineered cell surfaces are composed of bioconjugates embedded in liposome membranes, surface-immobilized bilayers, or the plasma membranes of living cells. This review article summarizes the various ways that Nature anchors integral and peripheral proteins in a cell membrane and describes the strategies devised by chemical biologists to label a membrane protein in living cells. Also discussed are modern synthetic and semisynthetic methods to produce lipidated proteins. Subsequent sections describe methods to anchor a three-component synthetic construct that is composed of a lipophilic membrane anchor, hydrophilic linker, and exposed functional component. The surface exposed payload can be a fluorophore, aptamer, oligonucleotide, polypeptide, peptide nucleic acid, polysaccharide, branched dendrimer, or linear polymer. Hydrocarbon chains are commonly used as the membrane anchor, and a general experimental trend is that a two chain lipid anchor has higher membrane affinity than a cholesteryl or single chain lipid anchor. Amphiphilic fluorescent dyes are effective molecular probes for cell membrane imaging and a zwitterionic linker between the fluorophore and the lipid anchor promotes high persistence in the plasma membrane of living cells. A relatively new advance is the development of switchable membrane anchors as molecular tools for fundamental studies or as technology platforms for applied biomaterials.
摘要:
广泛的生物材料和工程化细胞表面由嵌入脂质体膜中的生物缀合物组成,表面固定的双层,或活细胞的质膜。这篇综述文章总结了Nature在细胞膜中锚定整合蛋白和外周蛋白的各种方式,并描述了化学生物学家设计的标记活细胞中膜蛋白的策略。还讨论了生产脂化蛋白的现代合成和半合成方法。随后的部分描述了锚定由亲脂性膜锚组成的三组分合成构建体的方法。亲水接头,和暴露的功能组件。表面暴露的有效载荷可以是荧光团,适体,寡核苷酸,多肽,肽核酸,多糖,支化树枝状聚合物,或线性聚合物。烃链通常用作膜锚,和一般的实验趋势是双链脂质锚比胆固醇基或单链脂质锚具有更高的膜亲和力。两亲性荧光染料是用于细胞膜成像的有效分子探针,并且荧光团和脂质锚之间的两性离子接头促进活细胞的质膜中的高持久性。一个相对较新的进展是开发可转换膜锚作为基础研究的分子工具或作为应用生物材料的技术平台。