An Introduction to the Stickers-and-Spacers Framework as Applied to Biomolecular Condensates

Cellular organization is determined by a combination of membrane-bound and membrane-less biomolecular assemblies that range from clusters of tens of molecules to micrometer-sized cellular bodies. Over the last decade, membrane-less assemblies have come to be referred to as biomolecular condensates, reflecting their ability to condense specific molecules with respect to the remainder of the cell. In many cases, the physics of phase transitions provides a conceptual framework and a mathematical toolkit to describe the assembly, maintenance, and dissolution of biomolecular condensates. Among the various quantitative and qualitative models applied to understand intracellular phase transitions, the stickers-and-spacers framework offers an intuitive yet rigorous means to map biomolecular sequences and structure to the driving forces needed for higher-order assembly. This chapter introduces the fundamental concepts behind the stickers-and-spacers model, considers its application to different biological systems, and discusses limitations and misconceptions around the model.