Jeon Hyo Jae, Lee Joo Hyung, Park Ae Ji, Choi Jeong-Mo, Kang Kyungtae
Department of Applied Chemistry, Kyung Hee University, Yongin, Gyeonggi 17104, South Korea.
Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Republic of Korea.
Biomacromolecules. 2025 Feb 10;26(2):1075-1085. doi: 10.1021/acs.biomac.4c01410. Epub 2025 Jan 26.
This study proposes fluorenylmethoxycarbonyl (Fmoc)-protected single amino acids (Fmoc-AAs) as a minimalistic model system to investigate liquid-liquid phase separation (LLPS) and the elusive liquid-to-solid transition of condensates. We demonstrated that Fmoc-AAs exhibit LLPS depending on the pH and ionic strength, primarily driven by hydrophobic interactions. Systematic examination of the conditions under which each Fmoc-AA undergoes LLPS revealed distinct residue-dependent trends in the critical concentrations and phase behavior. Importantly, we elucidated the liquid-to-solid transition process, suggesting that it may be driven by a molecular mechanism different from that of LLPS. Fmoc-AA condensates showed promise for biomolecular enrichment and catalytic applications. This work provides significant insights into the molecular mechanisms of LLPS and the subsequent liquid-to-solid transition, offering a robust platform for future studies related to protocells and protein aggregation diseases.
本研究提出以芴甲氧羰基（Fmoc）保护的单个氨基酸（Fmoc-AA）作为一个简约的模型系统，用于研究液-液相分离（LLPS）以及凝聚物难以捉摸的液-固转变。我们证明，Fmoc-AA根据pH值和离子强度表现出LLPS，主要由疏水相互作用驱动。对每种Fmoc-AA发生LLPS的条件进行系统研究，揭示了临界浓度和相行为中不同的残基依赖性趋势。重要的是，我们阐明了液-固转变过程，表明其可能由不同于LLPS的分子机制驱动。Fmoc-AA凝聚物在生物分子富集和催化应用方面显示出前景。这项工作为LLPS的分子机制以及随后的液-固转变提供了重要见解，为未来与原始细胞和蛋白质聚集疾病相关的研究提供了一个强大的平台。
