Temperature-Triggered Nanoscale Morphological Transitions in a Synthetic Intrinsically Disordered Protein

IF 5.9 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2026-09-14 Epub Date: 2026-08-28 DOI:10.1021/acs.biomac.6c00295

Yulia Shmidov, Lixin Fan, Max Ney, Sonal Deshpande, Parul Sirohi, Joshua J Milligan, Ashutosh Chilkoti

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引用次数: 0

Abstract

Peptide self-assembly and liquid–liquid phase separation (LLPS), often mediated by intrinsically disordered regions (IDRs), are natural mechanisms that translate protein molecular features into complex nano- and mesoscale architectures. Although the thermodynamics and kinetics of these processes are well understood, synthetic materials integrating both functionalities remain rare. Inspired by the conserved IDR–assembly domain (AD) architecture of amyloidogenic proteins, we hypothesized that modular recombinant constructs combining LLPS-capable IDRs with β-sheet-forming ADs could generate materials with tunable structural properties. To test this, we engineered a library of elastin-like polypeptides (ELPs) fused to amphiphilic anionic or cationic amyloidogenic peptides, enabling systematic investigation of how sequence parametersincluding ELP length, AD charge, and hydrophilicityand environmental conditions, including temperature, pH, and salt concentration, influence material behavior. Our results reveal links between molecular design and emergent multiscale structures, including micelles and vesicles embedded within coacervates. This work provides a framework for designing hybrid proteins coupling LLPS and self-assembly.

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合成内在无序蛋白的温度触发纳米级形态转变

肽自组装和液-液相分离（LLPS）通常由内在无序区（IDRs）介导，是将蛋白质分子特征转化为复杂的纳米和中尺度结构的自然机制。虽然这些过程的热力学和动力学已经被很好地理解，但集成这两种功能的合成材料仍然很少。受淀粉样蛋白的保守didr组装结构域（AD）结构的启发，我们假设将llps -能力的idrs与β-片状形成的ADs结合起来的模块化重组构建物可以产生具有可调结构特性的材料。为了验证这一点，我们设计了一个弹性蛋白样多肽（ELP）的文库，将其融合到两亲性阴离子正规性淀粉样蛋白肽中，从而能够系统地研究序列参数（包括ELP长度、AD电荷和亲水性）和环境条件（包括温度、pH和盐浓度）如何影响材料行为。我们的研究结果揭示了分子设计和涌现的多尺度结构之间的联系，包括嵌在凝聚体中的胶束和囊泡。这项工作为设计偶联llps和自组装的杂交蛋白提供了一个框架。

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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.