Biomolecular condensates organize biochemistry, yet little is known about how cells control the position and scale of these structures. In cells, condensates often appear as relatively small assemblies that do not coarsen into a single droplet despite their propensity to fuse. Here, we report that ribonucleoprotein condensates of the glutamine-rich protein Whi3 interact with the endoplasmic reticulum, which prompted us to examine how membrane association controls condensate size. Reconstitution revealed that membrane recruitment promotes Whi3 condensation under physiological conditions. These assemblies rapidly arrest, resembling size distributions seen in cells. The temporal ordering of molecular interactions and the slow diffusion of membrane-bound complexes can limit condensate size. Our experiments reveal a trade-off between locally enhanced protein concentration at membranes, which favours condensation, and an accompanying reduction in diffusion, which restricts coarsening. Given that many condensates bind endomembranes, we predict that the biophysical properties of lipid bilayers are key for controlling condensate sizes throughout the cell.

生物分子凝聚物组织生物化学，但​​对细胞如何控制这些结构的位置和规模知之甚少。在细胞中，冷凝物通常表现为相对较小的组件，尽管它们倾向于融合，但不会粗化成单个液滴。在这里，我们报告富含谷氨酰胺的蛋白质 Whi3 的核糖核蛋白缩合物与内质网相互作用，这促使我们研究膜结合如何控制缩合物的大小。重构显示膜募集促进生理条件下的 Whi3 凝聚。这些组件迅速停止，类似于在细胞中看到的尺寸分布。分子相互作用的时间顺序和膜结合复合物的缓慢扩散可以限制冷凝物的大小。我们的实验揭示了膜上局部增强的蛋白质浓度之间的权衡，这有利于冷凝，以及伴随的扩散减少，这限制了粗化。鉴于许多冷凝物结合内膜，我们预测脂质双层的生物物理特性是控制整个细胞的冷凝物大小的关键。