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.

中文翻译：

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脂质-蛋白质探戈的电子摄像

从酶催化到突触传递的生物现象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，在没有探针或标签的情况下直接对这些纳米级动力学进行成像一直是一个基本的方法学挑战。在这里，我们开发了一种“电子摄像”方法——将液相电子显微镜与分子建模相结合——用这种方法我们拍摄了液体中单个、悬浮和未标记的膜蛋白纳米盘的纳米级结构波动。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充分减少照明电子束的影响，从而产生纳米级脂质-蛋白质相互作用的定量指纹。我们的结果表明，脂质-蛋白质相互作用在意想不到的长范围内描绘了动态修饰的膜域。此外，它们以特定于内部蛋白质的方式对整个纳米盘的分子力学做出了贡献。总的来说，这项工作展示了一种在纳米尺度上拍摄、量化和理解生物分子动力学的实验方法。