Abstract

Multivalent biopolymers phase separate into membrane-less organelles (MLOs) which exhibit liquid-like behavior. Here, we explore formation of prototypical MOs from multivalent proteins on various time and length scales and show that the kinetically arrested metastable multi-droplet state is a dynamic outcome of the interplay between two competing processes: a diffusion-limited encounter between proteins, and the exhaustion of available valencies within smaller clusters. Clusters with satisfied valencies cannot coalesce readily, resulting in metastable, long-living droplets. In the regime of dense clusters akin to phase-separation, we observe co-existing assemblies, in contrast to the single, large equilibrium-like cluster. A system-spanning network encompassing all multivalent proteins was only observed at high concentrations and large interaction valencies. In the regime favoring large clusters, we observe a slow-down in the dynamics of the condensed phase, potentially resulting in loss of function. Therefore, metastability could be a hallmark of dynamic functional droplets formed by sticker-spacer proteins.

Data availability

All data generated and analyzed are included in the manuscript and supporting files.

Article and author information

Author details

  1. Srivastav Ranganathan

    Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Eugene I Shakhnovich

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    For correspondence
    shakhnovich@chemistry.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4769-2265

Funding

National Institutes of Health (RO1 GM068670)

  • Eugene I Shakhnovich

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Rohit V Pappu, Washington University in St Louis, United States

Version history

  1. Received: February 19, 2020
  2. Accepted: June 1, 2020
  3. Accepted Manuscript published: June 2, 2020 (version 1)
  4. Version of Record published: July 14, 2020 (version 2)

Copyright

© 2020, Ranganathan & Shakhnovich

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Srivastav Ranganathan
  2. Eugene I Shakhnovich
(2020)
Dynamic metastable long-living droplets formed by sticker-spacer proteins
eLife 9:e56159.
https://doi.org/10.7554/eLife.56159

Share this article

https://doi.org/10.7554/eLife.56159

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