Multiphase Organization Is a Second Phase Transition Within Multi-Component Biomolecular Condensates

We present a mean-field theory for the multiphase organization of multi-component biomolecular condensates and validate the theory by molecular dynamics simulations of model mixtures. A first phase transition results in the separation of the dense phase from the bulk phase. In a second phase transition, the components in the dense phase demix to localize in separate regions that attach to each other. The second phase transition occurs when the strength of cross-species attraction goes below the mean strength of the self-attraction of the individual species and reaches a critical value. At a given strength of cross-species attraction, both of the phase transitions can be observed by decreasing temperature, leading first to phase separation and then to demixing of the dense phase. The theory and simulations establish the disparity in strength between self and cross-species attraction as a main driver for the multiphase organization of multi-component biomolecular condensates. TOC GRAPHICS O_FIG O_LINKSMALLFIG WIDTH=196 HEIGHT=200 SRC="FIGDIR/small/460104v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@e17fdcorg.highwire.dtl.DTLVardef@9168deorg.highwire.dtl.DTLVardef@7c07bcorg.highwire.dtl.DTLVardef@e0077d_HPS_FORMAT_FIGEXP M_FIG C_FIG