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High-throughput in situ single particle X-ray imaging of dehydrating viral capsids

Mall, Abhishek ; Munke, Anna LU orcid ; Mazumder, Parichita ; Shen, Zhou ; Bielecki, Johan ; E, Juncheng ; Estillore, Armando D. ; Kim, Chan ; Letrun, Romain and Lübke, Jannik , et al. (2026) In Light: Science & Applications 15.
Abstract
Single-stranded RNA viruses co-assemble their capsid with the genome, and variations in capsid structures can have significant functional relevance. In particular, viruses need to respond to a dehydrating environment to prevent genomic degradation and remain active upon rehydration. Theoretical work has predicted low-energy buckling transitions in icosahedral capsids, which could protect the virus from further dehydration. However, there has been no direct experimental evidence, nor a molecular mechanism, for such behavior. Here, we observe this transition using X-ray single particle imaging of MS2 bacteriophages after aerosolization. Using a combination of machine learning tools, we classify hundreds of thousands of single-particle... (More)
Single-stranded RNA viruses co-assemble their capsid with the genome, and variations in capsid structures can have significant functional relevance. In particular, viruses need to respond to a dehydrating environment to prevent genomic degradation and remain active upon rehydration. Theoretical work has predicted low-energy buckling transitions in icosahedral capsids, which could protect the virus from further dehydration. However, there has been no direct experimental evidence, nor a molecular mechanism, for such behavior. Here, we observe this transition using X-ray single particle imaging of MS2 bacteriophages after aerosolization. Using a combination of machine learning tools, we classify hundreds of thousands of single-particle diffraction patterns to learn the structural landscape of the capsid morphology as a function of time spent in the aerosol phase. We found a previously unreported compact conformation as well as intermediate structures that suggest an incoherent buckling transition that does not preserve icosahedral symmetry. Finally, we propose a mechanism for this buckling, where a single 19-residue loop is destabilized, leading to the large observed morphological change. Our results provide experimental evidence for a mechanism by which viral capsids may protect themselves from dehydration upon aerosolization. In the process, these findings also demonstrate the power of single-particle X-ray imaging and machine learning methods in studying biomolecular structural dynamics. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Light: Science & Applications
volume
15
article number
280
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:105042627902
DOI
10.1038/s41377-026-02262-0
language
English
LU publication?
yes
id
2a80f900-9353-4e63-a836-c2adb0edfdae
date added to LUP
2026-06-23 15:03:32
date last changed
2026-08-25 04:01:13
@article{2a80f900-9353-4e63-a836-c2adb0edfdae,
  abstract     = {{Single-stranded RNA viruses co-assemble their capsid with the genome, and variations in capsid structures can have significant functional relevance. In particular, viruses need to respond to a dehydrating environment to prevent genomic degradation and remain active upon rehydration. Theoretical work has predicted low-energy buckling transitions in icosahedral capsids, which could protect the virus from further dehydration. However, there has been no direct experimental evidence, nor a molecular mechanism, for such behavior. Here, we observe this transition using X-ray single particle imaging of MS2 bacteriophages after aerosolization. Using a combination of machine learning tools, we classify hundreds of thousands of single-particle diffraction patterns to learn the structural landscape of the capsid morphology as a function of time spent in the aerosol phase. We found a previously unreported compact conformation as well as intermediate structures that suggest an incoherent buckling transition that does not preserve icosahedral symmetry. Finally, we propose a mechanism for this buckling, where a single 19-residue loop is destabilized, leading to the large observed morphological change. Our results provide experimental evidence for a mechanism by which viral capsids may protect themselves from dehydration upon aerosolization. In the process, these findings also demonstrate the power of single-particle X-ray imaging and machine learning methods in studying biomolecular structural dynamics.}},
  author       = {{Mall, Abhishek and Munke, Anna and Mazumder, Parichita and Shen, Zhou and Bielecki, Johan and E, Juncheng and Estillore, Armando D. and Kim, Chan and Letrun, Romain and Lübke, Jannik and Rafie-Zinedine, Safi and Round, Adam and Round, Ekaterina and Rütten, Michael and Samanta, Amit K. and Sarma, Abhisakh and Sato, Tokushi and Schulz, Florian and Seuring, Carolin and Wollweber, Tamme and Worbs, Lena and Vagovic, Patrik and Bean, Richard and Mancuso, Adrian P. and Loh, Ne-Te Duane and Beck, Tobias and Küpper, Jochen and Maia, Filipe R.N.C. and Chapman, Henry N. and Ayyer, Kartik}},
  language     = {{eng}},
  month        = {{06}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Light: Science & Applications}},
  title        = {{High-throughput in situ single particle X-ray imaging of dehydrating viral capsids}},
  url          = {{http://dx.doi.org/10.1038/s41377-026-02262-0}},
  doi          = {{10.1038/s41377-026-02262-0}},
  volume       = {{15}},
  year         = {{2026}},
}