Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Orientating the Future Bio-Macromolecular Electron Microscopy

Version 1 : Received: 6 March 2018 / Approved: 6 March 2018 / Online: 6 March 2018 (07:17:15 CET)
Version 2 : Received: 2 May 2018 / Approved: 3 May 2018 / Online: 3 May 2018 (11:08:20 CEST)

A peer-reviewed article of this Preprint also exists.

Fei Sun. Orienting the future of bio-macromolecular electron microscopy[J]. Chin. Phys. B, 2018, 27(6):063601. Fei Sun. Orienting the future of bio-macromolecular electron microscopy[J]. Chin. Phys. B, 2018, 27(6):063601.


With forty years of developments, bio-macromolecule cryo-electron microscopy has met its revolution of resolution and is playing a very important role in structural biology study. According to different specimen states, cryo-electron microscopy (cryo-EM) involves three specific techniques, single particle analysis (SPA), electron tomography and sub-tomogram averaging, and electron diffraction. All these three techniques have not realized their full potentials of solving structures of bio-macromolecules and therefore need to be developed in the future. In this review, the current existing bottlenecks of cryo-EM SPA are discussed with theoretical analysis, which includes air-water interface during specimen cryo-vitrification, bio-macromolecular conformational heterogeneity, focus gradient within thick specimen, and electron radiation damage. Besides, potential solutions of these bottlenecks are proposed and discussed, which are worthy of further investigations in the future.


cryo-electron microscopy; air-water interface; conformational heterogeneity; focus gradient; radiation damage


Biology and Life Sciences, Biophysics

Comments (1)

Comment 1
Received: 6 March 2018
Commenter: Quan Wang
The commenter has declared there is no conflict of interests.
Comment: Excellent review with a well combination of rigorous theoretical reasoning and pragmatic perspective.
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