Modeling and Designing Particle-Regulated Amyloid-like Assembly of Synthetic Polypeptides in Aqueous Solution.
Modeling and Designing Particle-Regulated Amyloid-like Assembly of Synthetic Polypeptides in Aqueous Solution.
复制标题
水溶液中合成多肽的颗粒调节类淀粉样蛋白组装的建模和设计。
DOI：
10.1021/acs.biomac.1c01230
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发表时间：
2022
影响因子：
6.2
通讯作者：
Lin,Yao
中科院分区：
文献类型：
--
作者：
Yang,Tianjian;Benson,Kyle;Fu,Hailin;Xue,Tianrui;Song,Ziyuan;Duan,Hanyi;Xia,Hongwei;Kalluri,Ankarao;He,Jie;Cheng,Jianjun;Kumar,ChallaV;Lin,Yao
在细胞中，肌动蛋白和微管蛋白聚合受成核因子调节，成核因子以受控方式促进蛋白丝的成核和随后的生长。通过人工产生的成核因子来模仿这种自然机制来控制大分子单体的超分子聚合仍然是一个尚未解决的挑战。生物成核因子充当分子支架，提高蛋白质单体的局部浓度，并促进所需的构象变化，以加速成核和随后的聚合。本文演示了由阳离子二氧化硅纳米颗粒簇 (NPC) 作为人工成核因子催化的合成聚（L-谷氨酸）加速组装成淀粉样原纤维的过程，并建模为具有表面诱导异质成核途径的超分子聚合。原纤维生长的动力学研究与机械分析相结合表明，在其他相同的条件下，与非催化反应相比，人工成核剂可预见地将超分子聚合过程加速几个数量级（例如，将组装时间缩短 10 倍以上）。淀粉样蛋白样纤维性颤动得到了多种标准表征方法的支持。阳离子二氧化硅 NPC 的成核遵循类似 Michaelis-Menten 的方案，而相应的阴离子或中性纳米颗粒对原纤化没有影响。这种方法显示了电荷-电荷相互作用和表面官能团在促进大分子单体构象变化和控制原纤维生长成核速率方面的有效性。像这样的分子设计方法激发了通过仿生超分子聚合开发新型材料。
In cells, actin and tubulin polymerization is regulated by nucleation factors, which promote the nucleation and subsequent growth of protein filaments in a controlled manner. Mimicking this natural mechanism to control the supramolecular polymerization of macromolecular monomers by artificially created nucleation factors remains a largely unmet challenge. Biological nucleation factors act as molecular scaffolds to boost the local concentrations of protein monomers and facilitate the required conformational changes to accelerate the nucleation and subsequent polymerization. An accelerated assembly of synthetic poly(l-glutamic acid) into amyloid fibrils catalyzed by cationic silica nanoparticle clusters (NPCs) as artificial nucleation factors is demonstrated here and modeled as supramolecular polymerization with a surface-induced heterogeneous nucleation pathway. Kinetic studies of fibril growth coupled with mechanistic analysis demonstrate that the artificial nucleators predictably accelerate the supramolecular polymerization process by orders of magnitude (e.g., shortening the assembly time by more than 10 times) when compared to the uncatalyzed reaction, under otherwise identical conditions. Amyloid-like fibrillation was supported by a variety of standard characterization methods. Nucleation followed a Michaelis–Menten-like scheme for the cationic silica NPCs, while the corresponding anionic or neutral nanoparticles had no effect on fibrillation. This approach shows the effectiveness of charge–charge interactions and surface functionalities in facilitating the conformational change of macromolecular monomers and controlling the rates of nucleation for fibril growth. Molecular design approaches like these inspire the development of novel materials via biomimetic supramolecular polymerizations.