Optical Control of Membrane Viscosity Modulates ER-to-Golgi Trafficking
The lipid composition of cellular membranes is highly dynamic and undergoes continuous remodeling, affecting the biophysical properties critical to biological function. Here, we introduce an optical approach to manipulate membrane viscosity based on an exogenous synthetic fatty acid with an azobenzene photoswitch, termed <b>FAAzo4</b>. Cells rapidly incorporate <b>FAAzo4</b> into phosphatidylcholine and phosphatidylethanolamine in a concentration- and cell type-dependent manner. This generates photoswitchable PC and PE analogs, which are predominantly located in the endoplasmic reticulum. Irradiation causes a rapid photoisomerization that decreases membrane viscosity with high spatiotemporal precision. We use the resulting "PhotoCells" to study the impact of membrane viscosity on ER-to-Golgi transport and demonstrate that this two-step process has distinct membrane viscosity requirements. Our approach provides an unprecedented way of manipulating membrane biophysical properties directly in living cells and opens novel avenues to probe the effects of viscosity in a wide variety of biological processes.
Authors
- Sergio López (ORCID: https://orcid.org/0000-0001-5952-3568)
- Jan Lipfert (ORCID: https://orcid.org/0000-0003-3613-7896)
- Christopher J. Arp (ORCID: https://orcid.org/0000-0002-5059-6178)
- Suihan Feng (ORCID: https://orcid.org/0000-0002-9205-0050)
- Stefanie D. Pritzl (ORCID: https://orcid.org/0000-0001-8649-9225)
- Howard Riezman (ORCID: https://orcid.org/0000-0003-4680-9422)
- T. HARAYAMA (ORCID: https://orcid.org/0000-0003-2255-4197)
- Martin Reynders (ORCID: https://orcid.org/0000-0001-7415-3649)
- Dirk H. Trauner (ORCID: https://orcid.org/0000-0002-6782-6056)
- Beatrix Ueberheide (ORCID: https://orcid.org/0000-0003-2512-0204)
- Johannes Morstein (ORCID: https://orcid.org/0000-0002-6940-288X)
- A. Novák (ORCID: https://orcid.org/0000-0002-3619-018X)
- Nynke A. Vepřek (ORCID: https://orcid.org/0000-0001-7301-265X)
- Antonino Asaro (ORCID: https://orcid.org/0000-0001-9610-5381)
- Noemi Jiménez‐Rojo (ORCID: https://orcid.org/0000-0001-6200-0434)
- Evgeny Kanshin (ORCID: https://orcid.org/0000-0001-7142-4554)
- Theobald Lohmueller (ORCID: https://orcid.org/0000-0003-2699-7067)
- Yun Xu (ORCID: https://orcid.org/0000-0002-5137-6070)
- Manuel Muñiz (ORCID: https://orcid.org/0000-0001-8011-6991)
Institutions
- University of the Sciences (US)
- Ikerbasque (ES)
- University of Geneva (CH)
- Augsburg University (US)
- California Institute of Technology (US)
- Inserm (FR)
- University of the Basque Country (ES)
- University of Augsburg (DE)
- Utrecht University (NL)
- Chinese Academy of Sciences (CN)
- University of the Arts (US)
- California University of Pennsylvania (US)
- Nanomaterials Research (United States) (US)
- Division of Chemistry (US)
- Institute of Microelectronics (CN)
- NCCR Chemical Biology - Visualisation and Control of Biological Processes Using Chemistry (CH)
- Instituto de Biomedicina de Sevilla (ES)
- Institute for Physics (US)
- Immune Regulation (United Kingdom) (GB)
- Bioengineering Center (RU)
- Hospital Universitario Virgen del Rocío (ES)
- Gold Skin Care Center (US)
- Institut de Pharmacologie Moléculaire et Cellulaire (FR)
- Institute of Infection and Immunity (CA)
- École Polytechnique Fédérale de Lausanne (CH)
- New York University (US)
- Universidad de Sevilla (ES)
- University of Pennsylvania (US)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- ACS Central Science
- Published
- 2025-08-12
- DOI
- https://doi.org/10.1021/acscentsci.5c00606
- Citations
- 4
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 3.64
Funders
- Alexander von Humboldt-Stiftung
- Deutsche Forschungsgemeinschaft
- Fondation Leducq
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Eusko Jaurlaritza
- Studienstiftung des Deutschen Volkes
- European Regional Development Fund
- Agencia Estatal de Investigación
- National Key Research and Development Program of China
- National Cancer Institute
- National Institute of General Medical Sciences