A Single Amino Acid Model for Hydrophobically Driven Liquid–Liquid Phase Separation

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomacromolecules Pub Date : 2025-02-10 Epub Date: 2025-01-27 DOI:10.1021/acs.biomac.4c01410

Hyo Jae Jeon , Joo Hyung Lee , Ae Ji Park , Jeong-Mo Choi , Kyungtae Kang

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Abstract

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.

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疏水驱动液-液相分离的单氨基酸模型。

本研究提出氟酰甲氧羰基（Fmoc）保护的单氨基酸（Fmoc- aas）作为极简模型系统来研究液-液相分离（LLPS）和凝析油难以捉摸的液-固转变。我们证明了Fmoc-AAs表现出LLPS取决于pH和离子强度，主要是由疏水相互作用驱动的。对每个Fmoc-AA经历LLPS的条件进行系统检查，揭示了临界浓度和相行为的明显残留物依赖趋势。重要的是，我们阐明了液体到固体的转变过程，表明它可能是由不同于LLPS的分子机制驱动的。Fmoc-AA凝聚物具有生物分子富集和催化应用前景。这项工作为LLPS的分子机制和随后的液固转化提供了重要的见解，为未来与原细胞和蛋白质聚集性疾病相关的研究提供了一个强大的平台。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.