Endogenous biomolecular condensates, composed of a multitude of proteins and RNAs, can organize into multiphasic structures with compositionally distinct phases. This multiphasic organization is generally understood to be critical for facilitating their proper biological function. However, the biophysical principles driving multiphase formation are not completely understood. Here we use in vivo condensate reconstitution experiments and coarse-grained molecular simulations to investigate how oligomerization and sequence interactions modulate multiphase organization in biomolecular condensates. We demonstrate that increasing the oligomerization state of an intrinsically disordered protein results in enhanced immiscibility and multiphase formation. Interestingly, we find that oligomerization tunes the miscibility of intrinsically disordered proteins in an asymmetric manner, with the effect being more pronounced when the intrinsically disordered protein, exhibiting stronger homotypic interactions, is oligomerized. Our findings suggest that oligomerization is a flexible biophysical mechanism that cells can exploit to tune the internal organization of biomolecular condensates and their associated biological functions.

内源性生物分子凝聚物由多种蛋白质和 RNA 组成，可以组织成具有不同相的多相结构。人们普遍认为这种多相组织对于促进其正常的生物功能至关重要。然而，驱动多相形成的生物物理原理尚未完全了解。在这里，我们使用体内冷凝物重构实验和粗粒度分子模拟来研究寡聚和序列相互作用如何调节生物分子冷凝物中的多相组织。我们证明，增加本质上无序的蛋白质的寡聚状态会导致不混溶性和多相形成的增强。有趣的是，我们发现寡聚化以不对称方式调节本质无序蛋白质的混溶性，当表现出更强同型相互作用的本质无序蛋白质寡聚化时，效果更加明显。我们的研究结果表明，寡聚化是一种灵活的生物物理机制，细胞可以利用它来调整生物分子凝聚物的内部组织及其相关的生物功能。