Sorkin Benjamin, Wingreen Ned S
Princeton Center for Theoretical Science, Princeton University, Princeton, NJ 08544, USA.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
ArXiv. 2025 Jun 4:arXiv:2506.04493v1.
Phase separation of biomolecular condensates is ubiquitous in living cells, promoting colocalization of enzymes and their substrates as well as achieving membrane-free compartmentalization. Energy-consuming processes are routinely used to regulate biocondensate growth by opposing the thermodynamic tendency toward coarsening. At the same time, cells often use energy to instead accelerate thermodynamic processes. Here, we theoretically explore the possibility of utilizing chemical reactions to accelerate biocondensate coarsening. We combine Lifshitz-Slyozov theory with a reaction-diffusion approach, wherein particles interconvert between phase-separating and inert forms. We find that mass conservation restricts the volume growth to be linear in time (as in the passive case) despite activity, though if reactions are restricted to occur only outside droplets, the rate of Ostwald ripening can be increased by an arbitrarily large factor. Our acceleration theory is quantitatively supported by recent experiments on ripening in the presence of fueled interconversion reactions, under precisely the predicted conditions. We posit that the ability to induce rapid biocondensate coarsening can be advantageous in synthetic-biological contexts as a regulator of metabolic channeling.
生物分子凝聚物的相分离在活细胞中普遍存在，它促进了酶及其底物的共定位，并实现了无膜区室化。通过对抗粗化的热力学趋势，耗能过程通常被用于调节生物凝聚物的生长。与此同时，细胞常常利用能量来加速热力学过程。在此，我们从理论上探索利用化学反应加速生物凝聚物粗化的可能性。我们将利夫希茨 - 斯廖佐夫理论与反应扩散方法相结合，其中粒子在相分离形式和惰性形式之间相互转化。我们发现，尽管存在活性，但质量守恒限制了体积增长在时间上呈线性（如同被动情况），不过如果反应被限制仅在液滴外部发生，奥斯特瓦尔德熟化速率可以增大任意倍数。我们的加速理论在精确预测的条件下，得到了近期关于在存在燃料驱动的相互转化反应时熟化的实验的定量支持。我们认为，诱导生物凝聚物快速粗化的能力在合成生物学背景下作为代谢通道的调节剂可能具有优势。
