The effect of cell to cell variablilty in multicomponent protein phase separation

Proteins form biomolecular condensates inside cells which contribute to multiple cellular processes and regulatory mechanisms. These condensates, also called membrane-less organelles or cellular puncta, are formed by spontaneous condensation of biomolecules into liquid droplets. Interestingly, most toxic phase separation is the result of multicomponent protein phase separation. Given that concentrations of proteins vary substantially from cell to cell, we investigated how cellular variability affects protein phase separation. To that end, we studied a hypothetical two component protein system in which the primary proteins undergoes phase separation due to weak interaction with an adapter protein. Using Flory-Huggins theory and realistic values of variation in cellular proteins, our model predicts that the cell-to-cell heterogeneity of the adapter protein results the different threshold concentrations for primary proteins to phase separate. We observe that there is no clear cut-off concentration threshold of primary protein for the puncta formation as in single component protein system. Other results are discussed as well.