Kinetic solubility: how interaction persistence shapes cellular organization

Simon Alberti, Professor of Cellular Biochemistry at BIOTEC Dresden, Germany

Cells contain abundant multivalent proteins and nucleic acids, yet only selected molecules assemble into condensates. What prevents widespread assembly while permitting organization at specific locations and times? We propose kinetic solubility as a framework for understanding this selectivity through the interplay of macromolecular flux, interaction renewal, and kinetic reset.

A central distinction is between the lifetime of an individual bond and the persistence of an interaction state. Following dissociation, nearby partners can repeatedly rebind before escaping. Multivalency, polymer architecture, spatial confinement, and network topology can therefore sustain local association even when individual contacts are short-lived. In cells, macromolecular flux generates interaction-competent states, while energy-dependent remodeling and turnover limit their duration and capacity for renewal.

Using mRNA organization as an illustrative example, we discuss how translation and RNA remodeling constrain assembly-promoting interactions, and how changes in these processes can favor collective assembly. We propose that condensates can emerge when interaction renewal sustains network connectivity despite molecular exchange and kinetic reset.

This framework complements thermodynamic descriptions by addressing whether accessible assemblies form and persist on biological timescales. It predicts that altering reset activity can change cellular organization without requiring changes in intrinsic affinity or total macromolecular concentration. Interaction persistence thus provides a proposed link between molecular binding dynamics and the selective formation of higher-order cellular assemblies.