Modeling and Designing Particle-Regulated Amyloid-like Assembly of Synthetic Polypeptides in Aqueous Solution

Tianjian Yang, Kyle Benson, Hailin Fu, Tianrui Xue, Ziyuan Song, Hanyi Duan, Hongwei Xia, Ankarao Kalluri, Jie He, Jianjun Cheng, Challa V. Kumar, Yao Lin

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)196-209
Number of pages14
Issue number1
StatePublished - Jan 10 2022

ASJC Scopus subject areas

  • Bioengineering
  • Materials Chemistry
  • Polymers and Plastics
  • Biomaterials


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