1] Biology and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, USA [2] School of Natural Sciences, University of California, Merced, California 95340, USA [3] The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
1] Biology and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, USA [2] The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA [3] Mechanical Engineering Department, University of California, Berkeley, California 94720, USA.
Nature. 2014 Oct 30;514(7524):612-5. doi: 10.1038/nature13817.
There is much interest in developing synthetic analogues of biological membrane channels with high efficiency and exquisite selectivity for transporting ions and molecules. Bottom-up and top-down methods can produce nanopores of a size comparable to that of endogenous protein channels, but replicating their affinity and transport properties remains challenging. In principle, carbon nanotubes (CNTs) should be an ideal membrane channel platform: they exhibit excellent transport properties and their narrow hydrophobic inner pores mimic structural motifs typical of biological channels. Moreover, simulations predict that CNTs with a length comparable to the thickness of a lipid bilayer membrane can self-insert into the membrane. Functionalized CNTs have indeed been found to penetrate lipid membranes and cell walls, and short tubes have been forced into membranes to create sensors, yet membrane transport applications of short CNTs remain underexplored. Here we show that short CNTs spontaneously insert into lipid bilayers and live cell membranes to form channels that exhibit a unitary conductance of 70-100 picosiemens under physiological conditions. Despite their structural simplicity, these 'CNT porins' transport water, protons, small ions and DNA, stochastically switch between metastable conductance substates, and display characteristic macromolecule-induced ionic current blockades. We also show that local channel and membrane charges can control the conductance and ion selectivity of the CNT porins, thereby establishing these nanopores as a promising biomimetic platform for developing cell interfaces, studying transport in biological channels, and creating stochastic sensors.
人们对于开发高效且具有精细选择性的合成生物膜通道模拟物很感兴趣，以便用于离子和分子的传输。自上而下和自下而上的方法都可以产生与内源性蛋白通道相当大小的纳米孔，但复制它们的亲和力和传输特性仍然具有挑战性。从原则上讲，碳纳米管（CNT）应该是一种理想的膜通道平台：它们具有出色的传输性能，其狭窄的疏水性内孔模拟了生物通道的典型结构基序。此外，模拟预测，长度与脂质双层膜厚度相当的 CNT 可以自行插入膜中。功能化的 CNT 确实已被发现能够穿透脂质膜和细胞壁，并且短管已被强制插入膜中以制造传感器，但短 CNT 的膜传输应用仍未得到充分探索。在这里，我们表明短 CNT 可自发插入脂质双层和活细胞膜中，形成通道，在生理条件下其电导为 70-100 皮西门子。尽管结构简单，但这些“CNT 孔蛋白”可以随机切换亚稳定电导状态，传输水、质子、小离子和 DNA，并表现出特征性的大分子诱导离子电流阻塞。我们还表明，局部通道和膜电荷可以控制 CNT 孔蛋白的电导和离子选择性，从而将这些纳米孔确立为开发细胞界面、研究生物通道传输以及创建随机传感器的有前途的仿生平台。
