Mass spectrometric detection of protein nanoclusters: the invisible intermediates of phase separation
Phase separation of biomolecules, including intrinsically disordered proteins, is an underlying physical process behind cellular condensate formation. To increase mechanistic understanding of its initial stages, we demonstrate the application of charge detection mass spectrometry to characterise the mass dispersion of protein nanoclusters that represent intermediates in this important biophysical process. We detect polydisperse clusters of 1-280 protein molecules (64 kDa-18.4 MDa), that are currently invisible to most analytical techniques.
Authors
- Thuy Phuong Dao (ORCID: https://orcid.org/0000-0002-2168-7679)
- Carlos A. Castañeda (ORCID: https://orcid.org/0000-0001-9634-0867)
- Christina Glen Robb (ORCID: https://orcid.org/0009-0002-3825-0059)
- Jakub Ujma (ORCID: https://orcid.org/0000-0002-2751-7750)
- Rebecca Beveridge (ORCID: https://orcid.org/0000-0003-0320-6496)
- Anisha Haris (ORCID: https://orcid.org/0000-0002-6481-2580)
Institutions
- Waters (United States) (US)
- University of Strathclyde (GB)
- Syracuse University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-10-30
- DOI
- https://doi.org/10.64898/2026.10.28.762497
- Primary Topic
- Mass Spectrometry Techniques and Applications
- Type
- preprint
Funders
- UK Research and Innovation
- Leverhulme Trust
- National Institutes of Health