posted on 2021-12-29, 15:40authored byTianjian Yang, Kyle Benson, Hailin Fu, Tianrui Xue, Ziyuan Song, Hanyi Duan, Hongwei Xia, Ankarao Kalluri, Jie He, Jianjun Cheng, Challa V. Kumar, Yao Lin
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.