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.
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.
- Leslie M Loew
- Leslie M Loew
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Rohit V Pappu, Washington University in St Louis, United States
© 2021, Chattaraj et al.
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