Research Topic

Liquid phase electron microscopy of biological processes under physiological conditions

About this Research Topic

Microscopy methods are lacking that are capable of directly imaging the dynamic interactions of individual proteins and other biomolecules at the nanoscale. Liquid-phase electron microscopy (LP-EM), is capable of imaging cells in their native, liquid environment at nanometer resolution, which is sufficient to resolve individual proteins. But so far, visualizing biomolecular processes has been challenging because the required electron beam radiation level was three orders of magnitude above the known critical dose for causing damage to enzyme function, and the critical dose for reproductive cell death of most cells is even lower. Is it possible to image biological processes at the nanoscale with LP-EM, and how can one test if the observations reflect the nature of the underlying biological processes or are rather beam induced artifacts?

To achieve dynamic LP-EM of biomolecular processes under physiological conditions, key innovations in science and technology are needed. The first step is to bridge three orders of magnitude mismatch between the critical dose damaging protein function, and the minimum dose needed for nanometer spatial resolution. Could recently discover radiation damage mitigation mechanisms be employed, for example? Of key importance is to define critical standards for testing if the observed biological processes reflect the natural situation since it does not bring science forward much to report unknowingly results dominated by radiation artifacts. A key detail about the experiments needs to be reported such that other groups are able to reproduce and verify results. But most importantly is to design biological experiments that employ dynamic LP-EM to explore a possible new field in science. Being able to see things that were never seen before may lead to key discoveries in basic life science and biomedical research. For example, what would one learn when one would be able to directly observe a protein complex in the plasma membrane responding to ligand binding? How would it look like when a virus approaches and infects a cell? Many of the questions puzzling today’s cadre of scientists could possibly be answered at a glance.

Papers addressing the question of how to achieve dynamic LP-EM of biomolecular processes under physiological conditions, and examples of research of biological processes reflecting the natural situation (no radiation artifacts) studied at the nanoscale are of interest in this Research Topic. Topics include but not limited to:
• How can LP-EM be improved to overcome the radiation damage hurdle (e.g., phase plate, and detection technology, experimental design, time-resolved LP-EM)?
• What are the origins of radiation damage and how can radiation damage be mitigated?
• Sparse imaging techniques to reduce electron dose.
• How to define standards in the verification of native biological processes versus radiation artifacts?
• Examples of research in cell biology (bacteria, eukaryotic cells).
• Research on biomolecules, e.g., DNA, isolated proteins, and protein complexes.
• Biomineralization processes.
• Examples of live organisms imaging with LP-EM.


Keywords: Liquid Phase Electron Microscopy, LP-EM, live-cell imaging, protein imaging, microscopy, physiological conditions


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Microscopy methods are lacking that are capable of directly imaging the dynamic interactions of individual proteins and other biomolecules at the nanoscale. Liquid-phase electron microscopy (LP-EM), is capable of imaging cells in their native, liquid environment at nanometer resolution, which is sufficient to resolve individual proteins. But so far, visualizing biomolecular processes has been challenging because the required electron beam radiation level was three orders of magnitude above the known critical dose for causing damage to enzyme function, and the critical dose for reproductive cell death of most cells is even lower. Is it possible to image biological processes at the nanoscale with LP-EM, and how can one test if the observations reflect the nature of the underlying biological processes or are rather beam induced artifacts?

To achieve dynamic LP-EM of biomolecular processes under physiological conditions, key innovations in science and technology are needed. The first step is to bridge three orders of magnitude mismatch between the critical dose damaging protein function, and the minimum dose needed for nanometer spatial resolution. Could recently discover radiation damage mitigation mechanisms be employed, for example? Of key importance is to define critical standards for testing if the observed biological processes reflect the natural situation since it does not bring science forward much to report unknowingly results dominated by radiation artifacts. A key detail about the experiments needs to be reported such that other groups are able to reproduce and verify results. But most importantly is to design biological experiments that employ dynamic LP-EM to explore a possible new field in science. Being able to see things that were never seen before may lead to key discoveries in basic life science and biomedical research. For example, what would one learn when one would be able to directly observe a protein complex in the plasma membrane responding to ligand binding? How would it look like when a virus approaches and infects a cell? Many of the questions puzzling today’s cadre of scientists could possibly be answered at a glance.

Papers addressing the question of how to achieve dynamic LP-EM of biomolecular processes under physiological conditions, and examples of research of biological processes reflecting the natural situation (no radiation artifacts) studied at the nanoscale are of interest in this Research Topic. Topics include but not limited to:
• How can LP-EM be improved to overcome the radiation damage hurdle (e.g., phase plate, and detection technology, experimental design, time-resolved LP-EM)?
• What are the origins of radiation damage and how can radiation damage be mitigated?
• Sparse imaging techniques to reduce electron dose.
• How to define standards in the verification of native biological processes versus radiation artifacts?
• Examples of research in cell biology (bacteria, eukaryotic cells).
• Research on biomolecules, e.g., DNA, isolated proteins, and protein complexes.
• Biomineralization processes.
• Examples of live organisms imaging with LP-EM.


Keywords: Liquid Phase Electron Microscopy, LP-EM, live-cell imaging, protein imaging, microscopy, physiological conditions


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

25 January 2021 Abstract
25 May 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

25 January 2021 Abstract
25 May 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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