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Extending microsecond time-resolved cryo-electron microscopy with laser flash melting.

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Related Experiment Video

Updated: Jan 24, 2026

Preparation of High-Temperature Sample Grids for Cryo-EM
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Ultrathin liquid cells for microsecond time-resolved cryo-EM.

Wyatt A Curtis1, Jakub Wenz1,2, Constantin R Krüger1

  • 1Laboratory of Molecular Nanodynamics, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Nature Communications
|January 22, 2026
PubMed
Summary

Researchers developed a new method using silicon dioxide membranes to extend time-resolved cryo-electron microscopy (cryo-EM) observations of protein dynamics. This breakthrough allows for longer observation windows, advancing the study of protein function at the microsecond scale.

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Area of Science:

  • Structural Biology
  • Biophysics
  • Biochemistry

Background:

  • Time-resolved cryo-electron microscopy (cryo-EM) aims to capture proteins in action.
  • Current limitations restrict observations to tens of microseconds due to sample instability under laser irradiation.
  • Observing protein dynamics is crucial for understanding protein function.

Purpose of the Study:

  • To extend the observation window of microsecond time-resolved cryo-EM.
  • To overcome the instability of thin liquid films during laser irradiation.
  • To enable near-atomic resolution imaging of transient protein configurations.

Main Methods:

  • Developed a technique using ultrathin silicon dioxide membranes to encapsulate cryo samples.
  • Utilized laser-induced flash melting to initiate protein dynamics within a controlled time window.
  • Applied time-resolved temperature jump experiments on the 50S ribosomal subunit.

Main Results:

  • Extended the observation window for time-resolved cryo-EM by an order of magnitude.
  • Achieved near-atomic spatial resolution reconstructions.
  • Successfully eliminated preferred particle orientation.
  • Gained new insights into the conformational landscape of the L1 stalk.

Conclusions:

  • The novel silicon dioxide membrane technique significantly enhances microsecond time-resolved cryo-EM capabilities.
  • This advancement bridges the gap towards millisecond timescale observations.
  • The method offers a powerful tool for studying dynamic biological processes at high resolution.