Merging-limited coarsening governs long-term stability of nanoscale condensates

Abstract

AbstractDroplet coarsening occurs in a variety of fields, characterized by the spontaneous growth of smaller droplets into larger ones to minimize their interfacial free energy and achieve global thermodynamic equilibrium. However, recent studies revealed that the coarsening is much suppressed in living cells where nanoscale biomolecular condensates with droplet-like behaviors maintain stable sizes over extended time periods. The mechanism underpinning such long-term stability of condensates remains poorly understood. Here, we experimentally observe that coacervate droplets of small sizes (tens to hundreds of nanometers) remain stable over hours with significantly slower coarsening rates than predicted by classic theories. Using scaling analysis and Monte Carlo simulations, we demonstrate that the anomalously stable coacervates can be explained by a merging-limited coarsening (MLC), in which merging probability among coacervates of sizes smaller than a critical valuebecomes markedly low, whereηis the internal viscosity and γ is the interfacial tension of droplets. We further develop an analytical model that quantitatively captures the coarsening dynamics of coacervates across different experimental conditions. More broadly, by constructing a viscosity-interfacial tension diagram, we find that many biological condensates intrinsically exhibit large critical sizes, making them prone to undergo slow coarsening through the MLC mechanism. Such merging-limited coarsening may represent a universal mechanism underlying condensate size control in synthetic systems and living cells.