Phase Separation of Multi-Valent Signaling Proteins

Abstract

Cells are organized on length scales from Angstroms to microns. However, the mechanisms by which Angstrom-scale molecular properties are translated to micron-scale macroscopic properties are not well understood. We have shown that interactions between multivalent proteins and multivalent ligands can cause liquid-liquid demixing phase transitions, resulting in formation of micron-sized liquid droplets in aqueous solution and micron-sized puncta on membranes. These transitions appear to occur concomitantly with sol-gel transitions to form large, dynamic polymers within the droplets/puncta. I will discuss how such transitions may control the spatial organization and biochemical activity of actin regulatory signaling pathways, and contribute to formation of PML nuclear bodies in the mammalian nucleus. Our data suggest a general mechanism by which cells may achieve micron-scale organization based on interactions between multivalent macromolecules.