Membrane-less organelles resulting from liquid–liquid phase separation of biopolymers into intracellular condensates control essential biological functions, including messenger RNA processing, cell signalling and embryogenesis^1,2,3,4. It has recently been discovered that several such protein condensates can undergo a further irreversible phase transition, forming solid nanoscale aggregates associated with neurodegenerative disease^5,6,7. While the irreversible gelation of protein condensates is generally related to malfunction and disease, one case where the liquid-to-solid transition of protein condensates is functional, however, is that of silk spinning^8,9. The formation of silk fibrils is largely driven by shear, yet it is not known what factors control the pathological gelation of functional condensates. Here we demonstrate that four proteins and one peptide system, with no function associated with fibre formation, have a strong propensity to undergo a liquid-to-solid transition when exposed to even low levels of mechanical shear once present in their liquid–liquid phase separated form. Using microfluidics to control the application of shear, we generated fibres from single-protein condensates and characterized their structural and material properties as a function of shear stress. Our results reveal generic backbone–backbone hydrogen bonding constraints as a determining factor in governing this transition. These observations suggest that shear can play an important role in the irreversible liquid-to-solid transition of protein condensates, shed light on the role of physical factors in driving this transition in protein aggregation-related diseases and open a new route towards artificial shear responsive biomaterials.

生物聚合物液-液相分离成细胞内冷凝物而产生的无膜细胞器控制着基本的生物学功能，包括信使 RNA 加工、细胞信号传导和胚胎发生^1,2,3,4。最近发现，几种这样的蛋白质凝聚物可以经历进一步的不可逆相变，形成与神经退行性疾病^5,6,7相关的固体纳米级聚集体。虽然蛋白质凝结物的不可逆胶凝通常与故障和疾病有关，但蛋白质凝结物从液体到固体的转变发挥作用的一个例子是丝纺^8,9. 丝原纤维的形成主要由剪切驱动，但尚不清楚是什么因素控制功能性缩合物的病理凝胶化。在这里，我们证明了四种蛋白质和一种肽系统，没有与纤维形成相关的功能，当暴露于甚至低水平的机械剪切时，一旦存在于它们的液-液相分离中，就有很强的经历液体到固体转变的倾向形式。我们使用微流体控制剪切力的应用，从单一蛋白质凝聚物中生成纤维，并将其结构和材料特性表征为剪切应力的函数。我们的结果揭示了通用主链-主链氢键约束是控制这种转变的决定性因素。