Inside cells, proteins complex with nucleic acids to form liquid droplets resulting from liquid–liquid phase separation. The presence of mutated proteins can change the state of these liquid droplets to solids or gels, triggering neurodegenerative diseases. The mechanism of the liquid to solid or gel transition is still unclear. Solutions of poly(l-ornithine-co-l-citrulline) (P_LOC) copolymers, which exhibit upper critical solution temperature-type behavior, change state upon cooling. In this study, we evaluated the effect of nucleic acids complexed with P_LOC on phase changes. In the presence of nucleic acids, such as polyC and polyU, P_LOC formed liquid droplets at low temperatures. The droplets dissolved at temperatures above the phase separation temperature. The phase separation temperature depended on the chemical structure of the nucleobase, implying that electrostatic and hydrogen bonding interactions between the nucleic acid and P_LOC influenced phase separation. Furthermore, the liquid droplets spontaneously changed to gel-like precipitates due to spontaneous release of nucleic acids from the complex. The rate of the liquid droplet-to-gel transition depended on the magnitude of electrostatic and hydrogen bonding interactions between P_LOC and nucleic acid. P_LOC complexed with mRNA also underwent a liquid droplet-to-gel transition upon the release of mRNA. This work provides insights into the mechanism of pathogenic transitions of the cellular droplets.

中文翻译：

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瓜氨酸多肽与核酸复合的自发液滴到凝胶的转变

在细胞内，蛋白质与核酸复合，形成液-液相分离产生的液滴。突变蛋白质的存在可以将这些液滴的状态改变为固体或凝胶，从而引发神经退行性疾病。液体到固体或凝胶转变的机制仍不清楚。聚（L-鸟氨酸-共-L-瓜氨酸）（PL _OC）共聚物的溶液表现出上临界溶液温度类型行为，在冷却时改变状态。_{在这项研究中，我们评估了与 P L} OC复合的核酸对相变的影响。在存在核酸（例如 PolyC 和 PolyU）的情况下，PL _OC在低温下形成液滴。液滴在高于相分离温度的温度下溶解。相分离温度取决于核碱基的化学结构，这意味着核酸和PL OC之间的静电和氢键相互作用_影响相分离。此外，由于核酸从复合物中自发释放，液滴自发地变成凝胶状沉淀物。液滴到凝胶转变的速率取决于 P _L OC 和核酸之间静电和氢键相互作用的大小。与 mRNA 复合的PLOC在 mRNA 释放后_也经历了液滴到凝胶的转变。这项工作提供了对细胞液滴致病转变机制的见解。