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Chin. Phys. B, 2018, Vol. 27(6): 063601    DOI: 10.1088/1674-1056/27/6/063601
Special Issue: TOPICAL REVIEW — Electron microscopy methods for emergent materials and life sciences
TOPICAL REVIEW—Electron microscopy methods for the emergent materials and life sciences Prev   Next  

Orienting the future of bio-macromolecular electron microscopy

Fei Sun(孙飞)1,2,3
1 Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
2 Center for Excellent, National Laboratory of Biomacromolecule, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
3 School of Life Science, University of Chinese Academy of Sciences, Beijing 101407, China
Abstract  

With 40 years of development, bio-macromolecule cryo-electron microscopy (cryo-EM) has completed its revolution in terms of resolution and currently plays a highly important role in structural biology study. According to different specimen states, cryo-EM involves three specific techniques:single-particle analysis (SPA), electron tomography and sub-tomogram averaging, and electron diffraction. None of these three techniques have realized their full potential for solving the structures of bio-macromolecules and therefore need additional development. In this review, the current existing bottlenecks of cryo-EM SPA are discussed with theoretical analysis, which include the air-water interface during specimen cryo-vitrification, bio-macromolecular conformational heterogeneity, focus gradient within thick specimens, and electron radiation damage. Furthermore, potential solutions of these bottlenecks worthy of further investigation are proposed and discussed.

Keywords:  cryo-electron microscopy      air-water interface      conformational heterogeneity      focus gradient      radiation damage  
Received:  04 March 2018      Revised:  02 May 2018      Accepted manuscript online: 
PACS:  36.20.-r (Macromolecules and polymer molecules)  
  68.37.Og (High-resolution transmission electron microscopy (HRTEM))  
  87.64.Ee (Electron microscopy)  
  87.80.-y (Biophysical techniques (research methods))  
Fund: 

Project supported by the Science Funds from the Chinese Academy of Sciences (Grant Nos.ZDKYYQ20170002 and XDB08030202) and the Science Funds from the Ministry of Science and Technology of China (Grant Nos.2017YFA0504700 and 2014CB910700).

Corresponding Authors:  Fei Sun     E-mail:  feisun@ibp.ac.cn

Cite this article: 

Fei Sun(孙飞) Orienting the future of bio-macromolecular electron microscopy 2018 Chin. Phys. B 27 063601

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