1. Cell Biology
  2. Structural Biology and Molecular Biophysics
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The solubility product extends the buffering concept to heterotypic biomolecular condensates.

  1. Aniruddha Chattaraj
  2. Michael L Blinov
  3. Leslie M Loew  Is a corresponding author
  1. University of Connecticut Health Center, United States
  2. University of Connecticut School of Medicine, United States
Research Article
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Cite this article as: eLife 2021;10:e67176 doi: 10.7554/eLife.67176

Abstract

Biomolecular condensates are formed by liquid-liquid phase separation (LLPS) of multivalent molecules. LLPS from a single ('homotypic') constituent is governed by buffering: above a threshold, free monomer concentration is clamped, with all added molecules entering the condensed phase. However, both experiment and theory demonstrate that buffering fails for the concentration dependence of multi-component ('heterotypic') LLPS. Using network-free stochastic modeling, we demonstrate that LLPS can be described by the solubility product constant (Ksp): the product of free monomer concentrations, accounting for the ideal stoichiometries governed by the valencies, displays a threshold above which additional monomers are funneled into large clusters; this reduces to simple buffering for homotypic systems. The Ksp regulates the composition of the dilute phase for a wide range of valencies and stoichiometries. The role of Ksp is further supported by coarse-grained spatial particle simulations. Thus, the solubility product offers a general formulation for the concentration dependence of LLPS.

Data availability

All the model files, Python scripts and a "Readme" description of all the contents are available in a public GitHub repository: https://github.com/achattaraj/Ksp_phase_separation.Also source data files are given for 7 figures that are part of the manuscript.

Article and author information

Author details

  1. Aniruddha Chattaraj

    Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7105-6621
  2. Michael L Blinov

    Center for Cell Analysis and Modeling, University of Connecticut School of Medicine, Farmington, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Leslie M Loew

    Center for Cell Analysis and Modeling, University of Connecticut School of Medicine, Farmington, United States
    For correspondence
    les@volt.uchc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1851-4646

Funding

National Institute of General Medical Sciences (R24 GM137787)

  • Leslie M Loew

National Institute of General Medical Sciences (R01 GM132859)

  • Leslie M Loew

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

Publication history

  1. Received: February 2, 2021
  2. Accepted: July 2, 2021
  3. Accepted Manuscript published: July 8, 2021 (version 1)
  4. Version of Record published: July 19, 2021 (version 2)

Copyright

© 2021, Chattaraj et al.

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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