Principles of Client Enrichment and Biochemical Memory in Biomolecular Condensates

Biomolecular condensates are usually organised by scaffold molecules that drive phase separation, while client molecules that cannot condense on their own become selectively enriched in the dense phase. Molecules inside condensates are also continually remodelled by biochemical reactions whose dynamics can depend on their history (non-Markovian). The talk asks how client enrichment feeds back on scaffold interactions to set condensate composition and phase behaviour, how biochemical memory arises naturally in condensates, and how that memory can make condensates self-propelled, using the role of condensates in focal adhesions as motivation.

The first part examines client enrichment in a reconstituted focal-adhesion system in which focal adhesion kinase (FAK) and a phosphorylated p130Cas-Nck-N-WASP network act as scaffolds and the adaptor protein paxillin acts as a client. An associative-polymer model predicts both single- and multi-condensate regimes with distinct scaffold compositions, while experimentally constrained parameters favour a single FAK-Cas-paxillin co-condensate biased toward FAK.

The second part introduces a model of active phase separation with non-Markovian reactions. Delayed reaction feedback destabilises stationary droplets: when the memory time becomes comparable to the reaction turnover time, condensates deform and spontaneously adopt a polar, self-propelled state. In systems of many droplets, persistent biochemical memory mediates alignment, producing polar flocks and, at higher concentrations, travelling labyrinths.

Together these results show how client enrichment, post-translational modifications and biochemical memory regulate condensate composition, phase behaviour and dynamics, giving rise to self-propulsion and collective organisation.