Phase-separated biomolecular condensates containing proteins and RNAs can assemble into higher-order structures by forming thermodynamically stable interfaces between immiscible phases. Using a minimal model of a protein/RNA interaction network, we demonstrate how a “shared” protein species that partitions into both phases of a multiphase condensate can function as a tunable surfactant that modulates the interfacial properties. We use Monte Carlo simulations and free-energy calculations to identify conditions under which a low concentration of this shared species is sufficient to trigger a wetting transition. We also describe a numerical approach based on classical density functional theory to predict concentration profiles and surface tensions directly from the model protein/RNA interaction network. Finally, we show that the wetting phase diagrams that emerge from our calculations can be understood in terms of a simple model of selective adsorption to a fluctuating interface. Our work shows how a low-concentration protein species might function as a biological switch for regulating multiphase condensate morphologies.

• Received 11 December 2023
• Accepted 31 May 2024

DOI:https://doi.org/10.1103/PRXLife.2.023013

Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

Published by the American Physical Society