Dynamic metastable long-living droplets formed by sticker-spacer proteins

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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.

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

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Srivastav Ranganathan

Chemistry and Chemical Biology, Harvard University, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
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.

"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.

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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.