Motif Sequences and Intracellular Phase Separation

Intrinsically Disordered Proteins (IDPs) lack a unique folded structure, and yet perform diverse and important functions inside cells. Recent work suggests that some IDPs promote the formation of membrane-less organelles via phase separation, helping cells spatially organize their biomolecules. Classical theories of phase separation focus on homopolymers, but IDPs have evolved particular sequences of interacting motifs. How does an IDP’s motif sequence determine its physical properties? We propose a statistical physics model of IDPs to elucidate the relationship between motif sequence, the phase boundary, and the partitioning of proteins between phases.

We find that motif sequences strongly influence the physical properties of model IDPs. Intuitively, each sequence has its own preference for inter- versus intra-protein bonds, which favor a condensed versus a dilute phase, respectively. As a result, the concentration of IDPs required for phase separation depends strongly on the motif sequence. Our work demonstrates the emergence of spatial order from conformational disorder, a process which may play a key role in intracellular organization.