Cells can dynamically organize reactions through the formation of biomolecular condensates. These viscoelastic networks exhibit complex material properties and mesoscale architectures, including the ability to form multiphase assemblies. It was shown previously that condensates with complex architectures may arise at equilibrium in multicomponent systems or in condensates that were driven out of equilibrium by changes in external parameters such as temperature. In this study, we demonstrate that the aging of initially homogeneous protein-RNA condensates can spontaneously lead to the formation of kinetically arrested double-emulsion and core-shell structures without changes in external variables such as temperature or solution conditions. By combining time-resolved fluorescence-based experimental techniques with simulations based on the Cahn-Hilliard theory, we show that, as the protein-RNA condensates age, the decrease of the relative strength of protein-RNA interactions induces the release of RNA molecules from the dense phase. In condensates exceeding a critical size, aging combined with slow diffusion of the macromolecules trigger nucleation of dilute phase inside the condensates, which leads to the formation of double-emulsion structures. These findings illustrate a new mechanism of formation of multicompartment condensates.

中文翻译：

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通过蛋白质-RNA 凝聚物的老化形成多室结构


细胞可以通过形成生物分子缩合物来动态组织反应。这些粘弹性网络表现出复杂的材料特性和中尺度结构，包括形成多相组装体的能力。前面已经表明，具有复杂结构的凝析油可能在多组分系统中处于平衡状态，也可能在因温度等外部参数的变化而失去平衡的凝析油中出现。在这项研究中，我们证明了最初均相蛋白质-RNA 缩合物的老化可以自发地导致动力学停滞的液和核壳结构的形成，而不会改变温度或溶液条件等外部变量。通过将基于时间分辨荧光的实验技术与基于 Cahn-Hilliard 理论的模拟相结合，我们表明，随着蛋白质-RNA 凝聚物的老化，蛋白质-RNA 相互作用的相对强度的降低会诱导 RNA 分子从致密相中释放。在超过临界尺寸的凝聚物中，老化与大分子的缓慢扩散相结合，会触发凝聚物内部稀相成核，从而导致液结构的形成。这些发现说明了多隔室冷凝物形成的新机制。