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Cryo-electron Microscopy01:28

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Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...
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Cryogenic Electron Microscopy Informed Molecular Dynamics Simulations to Investigate the Disulfide Hydrogel

Yuanming Song1,2, Zhaoxu Li1,3, Justin T Mulvey1,3

  • 1Center for Complex and Active Materials, University of California, Irvine, Irvine, CA, 92697, USA.

Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry
|March 3, 2025
PubMed
Summary

Disulfide hydrogels self-assemble into stable fibers. Molecular dynamics simulations reveal hydrogen bonds are key, with thiol precursors influencing stability for tunable material design.

Keywords:
cryo‐electron microscopyhydrogelimage simulationmolecular dynamics simulationsself‐assembly

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Area of Science:

  • Materials Science
  • Biomaterials Engineering
  • Chemical Physics

Background:

  • Disulfide hydrogels leverage cysteine-based redox systems for dynamic material design.
  • Reversible disulfide bond formation drives active self-assembly in these hydrogels.

Purpose of the Study:

  • To elucidate the molecular mechanisms behind the active self-assembly of disulfide hydrogels.
  • To investigate the structural and dynamic properties of disulfide-assembled fibers.
  • To provide strategies for designing tunable materials based on controlled assembly.

Main Methods:

  • Cryogenic electron microscopy (cryo-EM) for structural analysis of fibers.
  • All-atom molecular dynamics (MD) simulations with cryo-EM-informed restraints.
  • Validation of simulations using simulated cryo-EM images.

Main Results:

  • Cryo-EM revealed individual fibers with a consistent diameter of 5.4 nm.
  • MD simulations reproduced fiber dimensions, identifying hydrogen bonds as the primary stabilizing force.
  • The disulfide gelator (CSSC) primarily adopts an open conformation.
  • Intermolecular interactions were higher at 70% CSSC conversion than 100%.
  • Fibers remain hydrated, with thiol precursor (CSH) playing a role in transient phase stabilization.

Conclusions:

  • Hydrogen bonds and CSH-CSSC interplay are crucial for disulfide hydrogel fiber stability.
  • MD simulations accurately model disulfide hydrogel assembly, complementing experimental data.
  • Findings offer insights for engineering tunable dynamic materials through controlled self-assembly.