A topology framework for macromolecular complexes and condensates

Macromolecular assemblies such as protein complexes and protein/RNA condensates are involved in most fundamental cellular processes. The arrangement of subunits within these nano-assemblies is critical for their biological function and is determined by the topology of physical contacts within and between the subunits forming the complex. Describing the spatial arrangement of these interactions is of central importance to understand their functional and stability consequences. In this concept article, we propose a circuit topology-based formalism to define the topology of a complex consisting of linear polymeric chains with inter- and intrachain interactions. We apply our method to a system of model polymer chains as well as protein assemblies. We show that circuit topology can categorize different forms of chain assemblies. Our multi-chain circuit topology should aid analysis and predictions of mechanistic and evolutionary principles in the design of macromolecular assemblies.