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Altering the edge chemistry of bicelles with peptoids
Chemistry and Physics of Lipids ( IF 3.4 ) Pub Date : 2018-11-02 , DOI: 10.1016/j.chemphyslip.2018.10.004
Helya Najafi , Shannon L. Servoss

Cell function is tied to the interactions that occur within and across the cell membrane. Therefore, understanding membrane-affiliated interactions is important to many biomedical applications. Advancing the body of knowledge about these interactions will lead to discoveries in biomarker detection and therapeutic targets for disease detection and treatment. Model membrane systems are an effective way to study membrane proteins for such discoveries, allowing for stable protein structure and maintaining native activity. Bicelles, disc-shaped lipid bilayers created by combining long- and short-chain phospholipids, are the model membrane system of focus in this study. Bicelles are accessible from both sides and have a wide size range, which makes them attractive for studying membrane interactions without affecting function. In this work, bicelles were functionalized with peptoids to alter the edge chemistry. Peptoids are suitable for this application because of the large diversity of available side chain chemistries that can be easily incorporated in a sequence-specific manner. The peptoid sequence consists of three functional regions to promote insertion into the edge of bicelles. The insertion sequence at the C-terminus contains two alkyl chains and two hydrophobic, chiral aromatic groups that anchor into the bicelle edge. The facially amphipathic helix contains chiral aromatic groups on one side that interact with the lipid tails and positively charged groups on the other side, which interact with the lipid head groups. Thiol groups are included at the N-terminus to allow for visualization of peptoid location in the bicelle. Bicelle morphology and size were assessed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Peptoid location in the bicelle was determined by attachment of gold nanoparticles, which confirmed preferential incorporation of the peptoid into the bicelle edge with 82% specificity. Additionally, the peptoid-functionalized bicelles are of similar size and morphology to non-functionalized bicelles. Results from this study show that peptoid-functionalized bicelles are a promising model membrane system with potential applications in biosensors or bioseparations.



中文翻译:

用类肽改变细胞的边缘化学

细胞功能与细胞膜内和细胞膜之间发生的相互作用有关。因此,了解膜相关的相互作用对许多生物医学应用很重要。推进关于这些相互作用的知识体系将导致发现生物标志物以及疾病检测和治疗的治疗靶标。模型膜系统是研究膜蛋白用于此类发现的有效方法,可实现稳定的蛋白结构并保持天然活性。Bicelles是通过结合长链和短链磷脂形成的盘状脂质双层,是本研究的模型膜系统。Bicell可以从两侧进入,并且尺寸范围广,这使其在研究膜相互作用而又不影响功能的情况下具有吸引力。在这项工作中,Bicelles用类肽功能化以改变边缘化学。类肽适用于此应用,因为可用的侧链化学种类繁多,可以很容易地以序列特异性方式掺入。类肽序列由三个功能区组成,以促进插入双链细胞边缘。C末端的插入序列包含两个烷基链和两个疏水的,手性的芳香族基团,这些基团锚固在比塞勒边缘。面部两亲性螺旋在一侧包含与脂质尾部相互作用的手性芳族基团,在另一侧包含与脂质头部基团相互作用的带正电荷的基团。硫醇基团包括在N末端,以便可视化二倍体中类肽的位置。通过透射电子显微镜(TEM)和动态光散射(DLS)评估比塞勒的形态和大小。通过金纳米颗粒的附着来确定二倍体中类肽的位置,这证实了类肽以82%的特异性优先掺入到二倍体边缘中。另外,类肽功能化的双细胞具有与非功能化的双细胞相似的大小和形态。这项研究的结果表明,类肽功能化的Bicelles是一种有前途的模型膜系统,在生物传感器或生物分离中具有潜在的应用前景。类肽官能化的双细胞具有与非官能化的双细胞相似的大小和形态。这项研究的结果表明,类肽功能化的Bicelles是一种有前途的模型膜系统,在生物传感器或生物分离中具有潜在的应用前景。类肽官能化的双细胞具有与非官能化的双细胞相似的大小和形态。这项研究的结果表明,类肽功能化的Bicelles是一种有前途的模型膜系统,在生物传感器或生物分离中具有潜在的应用前景。

更新日期:2018-11-02
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