Figure 2.

Prediction of a mean-field theory that assumes SynGAP/PSD-95 complex coacervation is driven solely by favorable interactions among stoichiometric S₃P₂ complexes (Eq. 13). (a) Simplified schematic representation of S₃, P, and S₃P₂. The three S₃ PBMs and their connecting chain segments to the CC trimer (large pink circle, see Fig. 1a) are now shown as small red circles, the PDZ3-SH3-GK domains of P are now shown as a blue circle encased in a green rectangle, and the yellow and blue N-terminal chain segments in Fig. 1a are not depicted explicitly. Each S₃P₂ is enclosed by a dashed circle to underscore its role as a unit of phase-separation-driving interaction in the mean-field theory. (b) Schematic picture of a hypothetical SynGAP/PSD-95 condensed phase. The formulation in Eq. 13 stipulates that although unbound S₃ and P may be present in the condensed phase, phase separation is only driven by interactions between units of S₃P₂ (magenta dashed lines). These interunit favorable interactions may include binding of a PDZ/PBM of one S₃P₂ to the SH3-GK of another S₃P₂ as envisioned in Fig. 1, b and c. (c) Predicted phase diagram for this hypothetical scenario based upon Eq. 13, using ${\mathcal{K}}^0$ = 10⁻¹⁰ and χ = 1.5 as illustration. The boundary of binodal phase separation is shown by the light blue lines. Each of the dashed dark blue lines is a tie line indicating a pair of coexisting phases on the boundary of the phase-separated region. The overall volume constraint of ${\phi }_{{\mathsf{S}}_3}$ + φ_P ≤ 1 is marked by the solid black line with slope = −1 for ${\phi }_{{\mathsf{S}}_3}$ + φ_P = 1, whereas the ${\phi }_{{\mathsf{S}}_3}$/φ_P = 1/2 stoichiometric ratio of the S₃P₂ complex is indicated by the black solid line with slope = 1/2.