---
title: "Mass photometry reveals RNA-driven changes in tau condensate interactions"
id: "biorxiv-6-single-molecule-mass-measurements-uncover-shifting-rna-interactions-during"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-6-single-molecule-mass-measurements-uncover-shifting-rna-interactions-during"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.07.27.740926v1?rss=1"
published_at: "2026-07-27T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Mass photometry reveals RNA-driven changes in tau condensate interactions
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-6-single-molecule-mass-measurements-uncover-shifting-rna-interactions-during
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.07.27.740926v1?rss=1)
- **Published At:** 2026-07-27T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study uses single-molecule mass measurements by **mass photometry** to directly observe RNA–protein interactions in phase-separated protein systems. - Authors applied this approach to **tau** condensates to track how changing RNA concentration affects condensate behavior and molecular assemblies. - Increasing RNA concentration that promotes phase re-entry was associated with **RNA-mediated tau multimerization**, rather than simple charge neutralization. - Each tau monomer in these multimers binds a linear RNA sequence of roughly **30 nucleotides**, according to measurements reported by the authors. - Complementary techniques—**solution NMR** and **native mass spectrometry**—confirmed formation of stable complexes between RNA and tau. - The interactions mapped to the **basic proline-rich and repeat domains of tau**, described in the article as having a net charge of −29. - The authors argue mass photometry can discriminate between two mechanistic scenarios in RNA-mediated phase behavior: **coacervation driven by charge neutralization** versus **complex formation that drives phase re-entry**. - The work is presented as a methodological advance and demonstration of mass photometry’s utility as a complementary tool for studying **RNA-mediated phase separation**. - This is a preprint; the article has not undergone peer review. Competing interest: one author (MFH) is an employee of Refeyn Ltd. Funding sources are listed in the preprint.
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Hantke, Dilraj Lama, Ali Miserez, Axel Abelein, Michael Landreh doi: https://doi.org/10.64898/2026.07.27.740926 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. Axel Leppert 1 Uppsala University; Karolinska Institutet; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Axel%2BLeppert%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Leppert%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAxel%2BLeppert%2B) * [ORCID record for Axel Leppert](http://orcid.org/0000-0001-6223-3350 "Open in new tab") * For correspondence: axel.leppert@icm.uu.se Jesper Shiapan 1 Uppsala University; Karolinska Institutet; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jesper%2BShiapan%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Shiapan%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJesper%2BShiapan%2B) Irena Papageorgiou 2 Uppsala University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Irena%2BPapageorgiou%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Papageorgiou%20I&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AIrena%2BPapageorgiou%2B) Qi Ying Neo 3 Karolinska Institutet; Nanyang Technological University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Qi%2BYing%2BNeo%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Neo%20QY&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AQi%2BYing%2BNeo%2B) Cecilia Mörman 1 Uppsala University; Karolinska Institutet; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Cecilia%2BM%C3%B6rman%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=M%C3%B6rman%20C&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ACecilia%2BM%25C3%25B6rman%2B) Hannah Osterholz 2 Uppsala University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Hannah%2BOsterholz%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Osterholz%20H&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AHannah%2BOsterholz%2B) Petra Mészáros 2 Uppsala University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Petra%2BM%C3%A9sz%C3%A1ros%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=M%C3%A9sz%C3%A1ros%20P&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3APetra%2BM%25C3%25A9sz%25C3%25A1ros%2B) Max F. Hantke 4 Refeyn Ltd; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Max%2BF.%2BHantke%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Hantke%20MF&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMax%2BF.%2BHantke%2B) Dilraj Lama 5 Karolinska Institutet; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Dilraj%2BLama%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Lama%20D&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ADilraj%2BLama%2B) Ali Miserez 6 Nanyang Technological University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Ali%2BMiserez%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Miserez%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAli%2BMiserez%2B) Axel Abelein 7 Karolinska Institute; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Axel%2BAbelein%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Abelein%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAxel%2BAbelein%2B) Michael Landreh 8 Uppsala University; Karolinska Institute * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Michael%2BLandreh%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Landreh%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMichael%2BLandreh%2B) * [Abstract](https://www.biorxiv.org/content/10.64898/2026.07.27.740926v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5658940/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.07.27.740926v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5658940/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.07.27.740926v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5658940/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.07.27.740926v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5658940/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.07.27.740926v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5658940/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract RNA interactions are a key contributor to the formation and disassembly of intracellular protein condensates. Although some proteins utilize specific RNA-binding domains, these processes can also be mediated by charge interactions with intrinsically disordered regions. Due to the dynamic nature of these systems, investigating the underlying specificity and stoichiometry remains challenging. Here, we demonstrate that single-molecule mass measurements with mass photometry can capture RNA-protein interactions in phase-separated protein systems. Using the approach to investigate RNA-mediated phase shifts of tau condensates, we find that increasing the RNA concentration, which promotes phase re-entry, results in RNA-mediated tau multimerization, where each tau monomer binds a linear RNA sequence of approximately 30 nucleotides. Solution NMR and native mass spectrometry confirm the formation of stable complexes between RNA and the basic proline-rich and repeat domains of tau, which have a net charge of -29. Our findings demonstrate that mass photometry can distinguish between charge neutralization, which drives coacervation, and complex formation, which mediates phase re-entry, making it a highly complementary tool for the study of RNA-mediated phase separation. ### Competing Interest Statement MFH is an employee of Refeyn Ltd. ## Funder Information Declared Cancerfonden Swedish Research Council (VR) Knut and Alice Wallenberg Foundation Swedish Society for Medical Research Swedish Alzheimer Foundation Swedish Brain Foundation CIMED Karolinska Institutet Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-NC-ND 4.0 International license](http://creativecommons.org/licenses/by-nc-nd/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.07.27.740926v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/07/27/2026.07.27.740926.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.07.27.740926v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Single-molecule mass measurements uncover shifting RNA interactions during condensate phase transitions Axel Leppert, Jesper Shiapan, Irena Papageorgiou, Qi Ying Neo, Cecilia Mörman, Hannah Osterholz, Petra Mészáros, Max F. Hantke, Dilraj Lama, Ali Miserez, Axel Abelein, Michael Landreh bioRxiv 2026.07.27.740926; doi: https://doi.org/10.64898/2026.07.27.740926 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. Share This Article: Copy [![Twitter logo](https://www.biorxiv
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