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ER tethering and active transport govern condensate diffusion during hyperosmotic stress
Bisal Halder1,2, Guoming Gao1,3, Armin Ahnoud1
1Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI 48109, USA.
Biorxiv : the Preprint Server for Biology
|July 16, 2025
Summary
Hyperosmotic shock causes cell compression and biomolecular condensate formation. This study reveals these condensates remain dynamic and accessible, organized by ER attachment and active transport, challenging static cytosol models.
Area of Science:
- Cell Biology
- Biophysics
- Molecular Biology
Background:
- Hyperosmotic shock induces cell volume compression, leading to hyperosmotic phase separation (HOPS) condensate formation in cytoplasm and nucleoplasm.
- The dynamics and regulation of these biomolecular condensates under hyperosmotic stress are not well understood.
Purpose of the Study:
- To systematically characterize the dynamics of HOPS condensates in hyperosmotically compressed cells.
- To elucidate the mechanisms governing condensate movement and spatial organization.
Main Methods:
- Live-cell single-particle tracking (SPT) across various timescales.
- Measurement of spatial accessibility and organelle labeling.
- Reconstruction of cellular accessibility maps using genetically encoded multimeric nanoparticles (GEMs).
Main Results:
- HOPS condensates primarily exhibit sub-diffusion, with a small fraction showing super-diffusion.
- Sub-diffusion originates from endoplasmic reticulum (ER) attachment; super-diffusion is linked to microtubule-dependent active transport.
- Compressed cell cytoplasm remains highly accessible, lacking significant local corrals.
Conclusions:
- The cytosol in hyperosmotically compressed cells is dynamic and accessible, contrary to previous assumptions.
- Condensates are spatially organized via docking to membrane structures and intermittent long-range transport.
- Findings provide a model for spatiotemporal organization of condensates through cellular structures and processes.
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