Protein Phase Separation Provides Long-Term Memory of Transient Spatial Stimuli
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Abstract
Protein/RNA clusters arise frequently in spatially regulated biological processes, from the asymmetric distribution of P granules and PAR proteins in developing embryos to localized receptor oligomers in migratory cells. This co-occurrence suggests that protein clusters might possess intrinsic properties that make them a useful substrate for spatial regulation. Here, we demonstrate that protein droplets show a robust form of spatial memory, maintaining the spatial pattern of an inhibitor of droplet formation long after it has been removed. Despite this persistence, droplets can be highly dynamic, continuously exchanging monomers with the diffuse phase. We investigate the principles of biophysical spatial memory in three contexts: a computational model of phase separation; a novel optogenetic system where light can drive rapid, localized dissociation of liquid-like protein droplets; and membrane-localized signal transduction from clusters of receptor tyrosine kinases. Our results suggest that the persistent polarization underlying many cellular and developmental processes could arise through a simple biophysical process, without any additional biochemical feedback loops.
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Ostwald ripening is being slowed down or prevented by an opposing force closely linked to the nature of our droplets.
“In our experiments with either passive or active coacervate droplets, we did not observe any shrinkage of small droplets, suggesting that Ostwald ripening is being slowed down or prevented by an opposing force closely linked to the nature of our droplets28.”
From Active coacervate droplets are protocells that grow and resist Ostwald ripening (2021) · cites this paper as [28]
The STAR Methods passage on long-term simulations says that Ostwald ripening or final fusion may occur extremely slowly, or that active processes may prevent a single-droplet equilibrium. It does not identify an opposing force intrinsic to the droplets as the reason ripening slows or stops. The observation about passive and active coacervate droplets is the citing authors’ own experiment, not a finding attributed to this source. (LLM, conf=0.85)
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Self-citation
- Authors
- Dine, E., Gil, A. A., Uribe, G., Brangwynne, C. P., & Toettcher, J. E.
- Affiliations
- Princeton University (US)
- Corresponding author
- Toettcher, Jared E.
- Venue
- Cell Systems
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 6
- Issue
- 6
- Pages
- 655-663.e5
- ISSN
- 2405-4712 (ISSN-L)
- PMC
- PMC6023754
- OpenAlex
- W2952516695
- Cited by
- 182
- References
- 38
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 26 · 2023: 16 · 2022: 29 · 2021: 32 · 2020: 19 · 2019: 17 · 2018: 6
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Systems (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Stony Brook University
- Children's Hospital Los Angeles (DP2EB024247, U01DA040601)
- Doris Duke Charitable Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- protein phase separation, liquid-liquid phase separation, protein droplets, spatial memory, spatial regulation, receptor tyrosine kinase signaling, polarization, P granules, PAR proteins, asymmetric cell division
- MeSH terms
- Computer Simulation, Membrane Proteins, Neoplasm Proteins, Proteins, RNA, Organelles, Signal Transduction, Feedback, Physiological, Memory, Long-Term, Optogenetics, Spatial Memory
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