Non‐Equilibrium Polymerization of Cross‐β Amyloid Peptides for Temporal Control of Electronic Properties

Abstract

Hydrophobic collapse plays crucial roles in protein functions, from accessing the complex three‐dimensional structures of native enzymes to the dynamic polymerization of non‐equilibrium microtubules. However, hydrophobic collapse can also lead to the thermodynamically downhill aggregation of aberrant proteins, which has interestingly led to the development of a unique class of soft nanomaterials. There remain critical gaps in the understanding of the mechanisms of how hydrophobic collapse can regulate such aggregation. Demonstrated herein is a methodology for non‐equilibrium amyloid polymerization through mutations of the core sequence of Aβ peptides by a thermodynamically activated moiety. An out of equilibrium state is realized because of the negative feedback from the transiently formed cross‐β amyloid networks. Such non‐equilibrium amyloid nanostructures were utilized to access temporal control over its electronic properties.

Chemically Fueled Transient Geometry Changes in Diphenic Acids

“…8 Inspired by nature's example, nonbiological out-of-equilibrium behavior driven by chemical fuels has recently attracted considerable attention. [9][10][11] Recent work from Boekhoven, 12,13 our group, 14,15 Das, 16,17 and others 18,19 has shown that carbodiimides, typically EDC (N -(3-dimethylaminopropyl)-N -ethylcarbodiimide hydrochloride), are useful fuels for abiotic nonequilibrium behavior. In a typical system, aqueous carboxylic acids react with carbodiimides to form carboxylic anhydrides, which subsequently undergo hydrolysis to regenerate the original carboxylic acids.…”

On the use of catalysis to bias reaction pathways in out-of-equilibrium systems

“…The analogy to microtubules is also exemplied in follow-up works where the system shows designed negative feedback from the assembled structure, even harnessing temporal regulation of crossb amyloid network electronic properties. 27,28 Although this example from Das relies on organocatalysis, it is distinctly different from the simulation described here, because the catalyst (i.e. the histidine moiety) is integrated in the transient product.…”

“…Moreover, coupling catalysis to a dissipative CRN containing assembling products could give rise to unusual assembly behaviour and feedback. [26][27][28]44 Here, instead of using enzymes, with limited operational stability and high specicity, it would be recommended to start exploring small molecules and metal catalysts. This way organocatalysis in combination with metal catalysis in non-natural systems can play similar roles as enzymes in nature and provide new systems with a high degree of control and an adaptive character.…”

On the Use of Catalysis to Bias Reaction Pathways in out Of-Equilibrium Systems

“…The analogy to microtubules is also exemplified in follow-up works where the system shows designed negative feedback from the assembled structure, even harnessing temporal regulation of cross-β amyloid network electronic properties. 27,28 Although this example from Das relies on organocatalysis, it is distinctly different from the simulation described here, because the catalyst (i.e. the histidine moiety) is integrated in the transient product.…”