Motif Sequences and the Statistical Physics of 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 homogeneous polymers, 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, conformational disorder, and biological function.

We find that motif sequences strongly influence the statistical properties of model IDPs. Intuitively, each sequence has its own set of spatial conformations which determine the relative entropy of inter- and intra-protein bonds. 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.