Statistical and Biological Physics
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Delay-facilitated self-assembly in compartmentalized systems

Understanding how spatial separation and particle exchange govern self-assembly is crucial to biology and the design of biomolecular systems. Here, we uncover a robust mechanism—delay‑facilitated assembly—in which slow exchange between compartments with distinct reaction rates markedly increases both assembly speed and final yield. Using a minimal two‑compartment model, we show that rapid reactions in a high‑reactivity domain coupled to a slowly exchanging, low‑reactivity reservoir create cooperative dynamics via a separation of timescales. This opens regimes where slow exchange simultaneously minimizes completion time and maximizes yield—even when either compartment alone would not assemble.

2025_11_27_PNAS The mechanism is geometry‑agnostic and persists in spatially extended systems with diffusive transport. Crucially, it provides practical design levers: by tuning compartment volumes and exchange rates, one can program self‑assembly outcomes without altering local chemistry or finely tuned kinetics. Together, these results offer a conceptual framework for leveraging spatial separation to build reliable, high‑performance synthetic assemblies and suggest that natural systems may similarly exploit slow exchange to enhance the effectiveness and robustness of molecular assembly.

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