Biozentrum, University of Basel, Spitalstrasse 41, 4056 Basel, Switzerland.
Research Group CryoEM Technology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Cell. 2024 Feb 1;187(3):563-584. doi: 10.1016/j.cell.2024.01.005.
Biology spans a continuum of length and time scales. Individual experimental methods only glimpse discrete pieces of this spectrum but can be combined to construct a more holistic view. In this Review, we detail the latest advancements in volume electron microscopy (vEM) and cryo-electron tomography (cryo-ET), which together can visualize biological complexity across scales from the organization of cells in large tissues to the molecular details inside native cellular environments. In addition, we discuss emerging methodologies for integrating three-dimensional electron microscopy (3DEM) imaging with multimodal data, including fluorescence microscopy, mass spectrometry, single-particle analysis, and AI-based structure prediction. This multifaceted approach fills gaps in the biological continuum, providing functional context, spatial organization, molecular identity, and native interactions. We conclude with a perspective on incorporating diverse data into computational simulations that further bridge and extend length scales while integrating the dimension of time.
生物学跨越了长度和时间尺度的连续统。个别实验方法只能瞥见这个光谱的离散片段，但可以结合起来构建更全面的视图。在这篇综述中，我们详细介绍了最新的体积电子显微镜（vEM）和冷冻电子断层扫描（cryo-ET）的进展，它们可以结合起来，从大组织中细胞的组织到天然细胞环境内部的分子细节，跨越尺度可视化生物复杂性。此外，我们还讨论了将三维电子显微镜（3DEM）成像与多模态数据（包括荧光显微镜、质谱、单颗粒分析和基于人工智能的结构预测）相结合的新兴方法。这种多方面的方法填补了生物学连续统中的空白，提供了功能背景、空间组织、分子身份和天然相互作用。我们最后展望了将不同的数据纳入计算模拟中，进一步缩小和扩展长度尺度，同时整合时间维度。
