Plasma membrane order maps functional diversity in immune cells
Abstract Cell membranes undergo biophysical remodeling as an adaptation to the surroundings and to perform specific biological functions. However, the extent and relevance of such changes in human immune cells remain unknown, largely because of the lack of single-cell and multidimensional methodologies. Here we apply a cytometry-based method to fill this gap by combining biophysical profiling with simultaneous analysis of immune cell markers. This platform reveals notable cell-type-dependent plasma membrane order heterogeneity in immune cells. By sorting immune cells according to their membrane order and performing transcriptome and spatial surface proteome analyses together with functional tests, we show that plasma membrane order can be used to identify subsets of immune cells with distinct phenotypes and functional behaviors. Our findings demonstrate a broad heterogeneity of plasma membrane order in immune cells that will provide a more precise definition of immune cell states on the basis of their biophysical properties in health and disease.
Authors
- Erdinç Sezgin (ORCID: https://orcid.org/0000-0002-4915-388X)
- Valentina Carannante (ORCID: https://orcid.org/0000-0003-4464-7087)
- Luca Andronico (ORCID: https://orcid.org/0000-0002-4326-073X)
- Sarantis Giatrellis (ORCID: https://orcid.org/0009-0002-6412-0530)
- Yidan Jiang (ORCID: https://orcid.org/0000-0003-0804-7586)
- Björn Önfelt (ORCID: https://orcid.org/0000-0001-5178-7593)
- Jaromír Mikeš (ORCID: https://orcid.org/0000-0002-9941-7855)
- Franziska Ragaller (ORCID: https://orcid.org/0000-0002-4148-262X)
- Leonard L. de Boer (ORCID: https://orcid.org/0000-0002-9370-5290)
- Abishek Arora (ORCID: https://orcid.org/0000-0002-6149-4417)
- Petter Brodin (ORCID: https://orcid.org/0000-0002-8103-0046)
- Cenk Onur Gürdap (ORCID: https://orcid.org/0000-0002-5327-2523)
- Andrey S. Klymchenko (ORCID: https://orcid.org/0000-0002-2423-830X)
- Sofiia Iskrak
- Patrick A. Sandoz
- Anders Österborg
- Marcus Buggert
Institutions
- Uppsala University (SE)
- Centre National de la Recherche Scientifique (FR)
- Karolinska University Hospital (SE)
- Science for Life Laboratory (SE)
- Hammersmith Hospital (GB)
- Karolinska Institutet (SE)
- Laboratoire de Biophotonique et Pharmacologie (FR)
- European Molecular Biology Laboratory (DE)
- MRC London Institute of Medical Sciences (GB)
- Imperial College London (GB)
- Université de Strasbourg (FR)
- KTH Royal Institute of Technology (SE)
Publication Details
- Journal
- Nature Chemical Biology
- Published
- 2026-09-09
- DOI
- https://doi.org/10.1038/s41589-026-02322-x
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00