Abstract
Cellular condensates often consist of 10s to 100s of distinct interacting molecular species. Because of the complexity of these interactions, predicting the point at which they will undergo phase separation is daunting. Using experiments and computation, we therefore studied a simple model system consisting of polySH3 and polyPRM designed for pentavalent heterotypic binding. We tested whether the peak solubility product, or the product of the dilute phase concentration of each component, is a predictive parameter for the onset of phase separation. Titrating up equal total concentrations of each component showed that the maximum solubility product does approximately coincide with the threshold for phase separation in both experiments and models. However, we found that measurements of dilute phase concentration include small oligomers and monomers; therefore, a quantitative comparison of the experiments and models required inclusion of small oligomers in the model analysis. Even with the inclusion of small polyPRM and polySH3 oligomers, models did not predict experimental results. This led us to perform dynamic light scattering experiments, which revealed homotypic binding of polyPRM. Addition of this interaction to our model recapitulated the experimentally observed asymmetry. Thus, comparing experiments with simulation reveals that the solubility product can be predictive of the interactions underlying phase separation, even if small oligomers and low affinity homotypic interactions complicate the analysis.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.