Advanced Electron Microscopy Techniques and Applications Open access Peer reviewed

MemBrain v2: an end-to-end tool for the analysis of membranes in cryo-electron tomography

Lorenz Lamm, Simon Zufferey, Hanyi Zhang, Ricardo D. Righetto and 10 more

Nature Methods | Sep 8, 2026 | 178 citations

Abstract

Abstract

Cryo-electron tomography provides unique insights into macromolecular complexes in their native environments, yet membrane analysis remains a major bottleneck due to low signal-to-noise ratios, missing wedge artifacts and the complexity of membrane-associated particles. Existing tools often require extensive manual annotation, struggle with generalization across datasets and lack integrated solutions for segmentation, particle localization and quantitative analysis. We introduce MemBrain v2, a deep-learning-enabled framework that unifies these tasks into a streamlined pipeline. MemBrain-seg leverages a diverse, collaboratively generated training dataset and specialized model training strategies to achieve generalizable membrane segmentation across variable tomographic conditions. MemBrain-pick enables data-efficient localization of membrane-bound particles by integrating geometric constraints with deep learning, reducing the need for extensive manual annotation. MemBrain-stats provides quantitative insights into particle distributions, computing spatial metrics to analyze intramembrane particle organization. MemBrain v2 integrates seamlessly into cryo-electron tomography workflows, providing an accessible and structured approach to membrane analysis.

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Authors

Researchers on this paper

Lorenz Lamm

first | University of Basel | ORCID 0000-0003-0698-7769

Simon Zufferey

middle | University of Basel

Hanyi Zhang

middle | University of Basel | ORCID 0000-0003-0109-6481

Ricardo D. Righetto

middle | University of Basel | ORCID 0000-0003-4247-4303

Wojciech Wietrzyñski

middle | MRC Laboratory of Molecular Biology | ORCID 0000-0001-8898-2392

Kevin A. Yamauchi

middle | SIB Swiss Institute of Bioinformatics | ORCID 0000-0002-7818-1388

Alister Burt

middle | MRC Laboratory of Molecular Biology | ORCID 0000-0002-9341-2295

Ye Liu

middle | Helmholtz Munich | ORCID 0000-0002-1901-669X

Antonio Martínez-Sánchez

middle | German Cancer Research Center | ORCID 0000-0002-5865-2138

Sebastian Ziegler

middle | German Cancer Research Center | ORCID 0000-0002-1693-5586

Fabian Isensee

middle | German Cancer Research Center | ORCID 0000-0002-3519-5886

Julia A. Schnabel

middle | King's College London | ORCID 0000-0001-6107-3009

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Citation

BibTeX

@article{Lamm2026MemBrain,
  title = {MemBrain v2: an end-to-end tool for the analysis of membranes in cryo-electron tomography},
  author = {Lorenz Lamm and Simon Zufferey and Hanyi Zhang and Ricardo D. Righetto and Wojciech Wietrzyñski and Kevin A. Yamauchi and Alister Burt and Ye Liu and Antonio Martínez-Sánchez and Sebastian Ziegler and Fabian Isensee and Julia A. Schnabel and Benjamin D. Engel and Tingying Peng},
  journal = {Nature Methods},
  year = {2026},
  doi = {10.1038/s41592-026-03178-8},
  url = {https://doi.org/10.1038/s41592-026-03178-8}
}

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