Morton Danielle, Mortezaei Shahab, Yemenicioglu Sukru, Isaacman Michael J, Nova Ian C, Gundlach Jens H, Theogarajan Luke
Department of Electrical and Computer Engineering, University of California, Santa Barbara, CA, 93106.
Department of Physics, University of Washington, Seattle, WA 98195.
J Mater Chem B. 2015 Jul 7;3(25):5080-5086. doi: 10.1039/C5TB00383K.
Nanopores based on protein channels inserted into lipid membranes have paved the way towards a wide-range of inexpensive biosensors, especially for DNA sequencing. A key obstacle in using these biological ion channels as nanodevices is the poor stability of lipid bilayer membranes. Amphiphilic block copolymer membranes have emerged as a robust alternative to lipid membranes. While previous efforts have shown feasibility, we demonstrate for the first time the effect of polymer composition on MspA protein functionality. We show that membrane-protein interaction depends on the hydrophobic-hydrophilic ratio (f-ratio) of the block copolymer. These effects are particularly pronounced in asymmetric protein pores like MspA compared to the cylindrical α-Hemolysin pore. A key effect of membrane-protein interaction is the increased 1/f noise. After first showing increases in 1/f behaviour arise from increased substate activity, the noise power spectral density was used as a qualitative tool for understanding protein-membrane interactions in polymer membranes. Polymer compositions with f-ratios close to lipid membranes caused noise behaviour not observed in lipid membranes. However, by modifying the f-ratio using a modular synthetic approach, we were able to design a block copolymer exhibiting noise properties similar to a lipid membrane, albeit with better stability. Thus, by careful optimization, block copolymer membranes can emerge as a robust alternative for protein-pore based nano-biosensors.
插入脂质膜中的基于蛋白质通道的纳米孔为广泛的廉价生物传感器，尤其是用于DNA测序的生物传感器铺平了道路。将这些生物离子通道用作纳米器件的一个关键障碍是脂质双层膜的稳定性较差。两亲性嵌段共聚物膜已成为脂质膜的一种强大替代物。虽然先前的研究已证明其可行性，但我们首次证明了聚合物组成对MspA蛋白功能的影响。我们表明，膜-蛋白相互作用取决于嵌段共聚物的疏水-亲水平衡比（f比）。与圆柱形α-溶血素孔相比，这些效应在诸如MspA的不对称蛋白孔中尤为明显。膜-蛋白相互作用的一个关键效应是1/f噪声增加。在首先表明1/f行为的增加源于亚态活性的增加之后，噪声功率谱密度被用作理解聚合物膜中蛋白-膜相互作用的定性工具。f比接近脂质膜的聚合物组成导致了脂质膜中未观察到的噪声行为。然而，通过使用模块化合成方法改变f比，我们能够设计出一种具有与脂质膜相似噪声特性的嵌段共聚物，尽管其稳定性更好。因此，通过仔细优化，嵌段共聚物膜可以成为基于蛋白孔的纳米生物传感器的一种强大替代物。
