Biomolecular condensates, protein-rich and dynamic membrane-less organelles, play critical roles in a range of subcellular processes, including membrane trafficking and transcriptional regulation. However, aberrant phase transitions of intrinsically disordered proteins in biomolecular condensates can lead to the formation of irreversible fibrils and aggregates that are linked to neurodegenerative diseases. Despite the implications, the interactions underlying such transitions remain obscure. Here we investigate the role of hydrophobic interactions by studying the low-complexity domain of the disordered ‘fused in sarcoma’ (FUS) protein at the air/water interface. Using surface-specific microscopic and spectroscopic techniques, we find that a hydrophobic interface drives fibril formation and molecular ordering of FUS, resulting in solid-like film formation. This phase transition occurs at 600-fold lower FUS concentration than required for the canonical FUS low-complexity liquid droplet formation in bulk. These observations highlight the importance of hydrophobic effects for protein phase separation and suggest that interfacial properties drive distinct protein phase-separated structures.

生物分子凝聚体是富含蛋白质和动态的无膜细胞器，在一系列亚细胞过程中发挥着关键作用，包括膜运输和转录调节。然而，生物分子凝聚物中本质上无序的蛋白质的异常相变可能导致不可逆原纤维和聚集体的形成，这与神经退行性疾病有关。尽管有这些影响，但这种转变背后的相互作用仍然模糊。在这里，我们通过研究空气/水界面处无序“肉瘤融合”（FUS）蛋白的低复杂性结构域来研究疏水相互作用的作用。使用表面特异性显微镜和光谱技术，我们发现疏水界面驱动纤维形成和 FUS 分子排序，从而形成固体状薄膜。这种相变发生的 FUS 浓度比批量形成标准 FUS 低复杂性液滴所需浓度低 600 倍。这些观察结果强调了疏水效应对蛋白质相分离的重要性，并表明界面特性驱动不同的蛋白质相分离结构。