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Abstract：
Biological phenomena, from enzymatic catalysis to synaptic transmission, originate in the structural transformations of biomolecules and biomolecular assemblies in liquid water. However, directly imaging these nanoscopic dynamics without probes or labels has been a fundamental methodological challenge. Here, we developed an approach for \"electron videography\"-combining liquid phase electron microscopy with molecular modeling-with which we filmed the nanoscale structural fluctuations of individual, suspended, and unlabeled membrane protein nanodiscs in liquid. Systematic comparisons with biochemical data and simulation indicate the graphene encapsulation involved can afford sufficiently reduced effects of the illuminating electron beam for these observations to yield quantitative fingerprints of nanoscale lipid-protein interactions. Our results suggest that lipid-protein interactions delineate dynamically modified membrane domains across unexpectedly long ranges. Moreover, they contribute to the molecular mechanics of the nanodisc as a whole in a manner specific to the protein within. Overall, this work illustrates an experimental approach to film, quantify, and understand biomolecular dynamics at the nanometer scale.
摘要：
生物现象,从酶催化到突触传递，起源于液态水中生物分子和生物分子组装体的结构转变。然而,直接成像这些纳米动力学没有探针或标签一直是一个基本的方法学挑战。这里,我们开发了一种“电子摄像”的方法-将液相电子显微镜与分子建模相结合-我们拍摄了个体的纳米级结构波动，暂停,和液体中的未标记膜蛋白纳米盘。与生化数据和模拟的系统比较表明，所涉及的石墨烯封装可以为这些观察提供足够降低的照射电子束的影响，以产生纳米级脂质-蛋白质相互作用的定量指纹。我们的结果表明，脂质-蛋白质相互作用在出乎意料的长范围内描绘了动态修饰的膜结构域。此外，它们以特定于内部蛋白质的方式为整个纳米圆盘的分子力学做出贡献。总的来说,这项工作说明了电影的实验方法，量化、了解纳米尺度的生物分子动力学。
