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细胞表面聚糖的埃分辨率成像。

Ångström-resolution imaging of cell-surface glycans.

作者信息

Masullo Luciano A, Almahayni Karim, Pachmayr Isabelle, Honsa Monique, Heinze Larissa, Fritsche Sarah, Grabmayr Heinrich, Jungmann Ralf, Möckl Leonhard

机构信息

Max Planck Institute of Biochemistry, Planegg, Germany.

Max Planck Institute for the Science of Light, Erlangen, Germany.

出版信息

Nat Nanotechnol. 2025 Jul 28. doi: 10.1038/s41565-025-01966-5.

DOI:10.1038/s41565-025-01966-5
PMID:40721874
Abstract

Glycobiology is rooted in the study of monosaccharides, ångström-sized molecules that are the building blocks of glycosylation. Glycosylated biomolecules form the glycocalyx, a dense coat encasing every human cell with central relevance-among others-in immunology, oncology and virology. To understand glycosylation function, visualizing its molecular structure is fundamental. However, the ability to visualize the molecular architecture of the glycocalyx has remained challenging. Techniques such as mass spectrometry, electron microscopy and fluorescence microscopy lack the necessary cellular context, specificity and resolution. Here we combine resolution enhancement by sequential imaging with metabolic labelling, enabling the visualization of individual sugars within glycans on the cell surface, thus obtaining images of the glycocalyx with a spatial resolution down to 9 Å in an optical microscope.

摘要

糖生物学源于对单糖的研究,单糖是埃级大小的分子,是糖基化的基本组成部分。糖基化生物分子形成糖萼,这是一层包裹着每个人体细胞的致密外衣,在免疫学、肿瘤学和病毒学等领域具有核心意义。为了理解糖基化功能,可视化其分子结构至关重要。然而,可视化糖萼分子结构的能力仍然具有挑战性。质谱分析、电子显微镜和荧光显微镜等技术缺乏必要的细胞背景、特异性和分辨率。在这里,我们将顺序成像分辨率增强与代谢标记相结合,能够可视化细胞表面聚糖中的单个糖,从而在光学显微镜下获得空间分辨率低至9埃的糖萼图像。

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本文引用的文献

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Restoring protein glycosylation with GlycoShape.用 GlycoShape 恢复蛋白质糖基化。
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Direct optical measurement of intramolecular distances with angstrom precision.
直接以埃精度测量分子内距离。
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Toward drift-free high-throughput nanoscopy through adaptive intersection maximization.通过自适应交叉最大化实现无漂移高通量纳米显微镜技术
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Genetics of glycosylation in mammalian development and disease.哺乳动物发育和疾病中的糖基化遗传学。
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Spatial proteomics in neurons at single-protein resolution.单蛋白分辨率下神经元中的空间蛋白质组学。
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Direct observation of glycans bonded to proteins and lipids at the single-molecule level.在单分子水平上直接观察与蛋白质和脂质结合的聚糖。
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