Co-assembly between Fmoc Diphenylalanine and Diphenylalanine within a 3D Fibrous Viscous Network Confers Atypical Curvature and Branching.

Chakraborty, Priyadarshi; Tang, Yiming; Guterman, Tom; Arnon, Zohar A; Yao, Yifei; Wei, Guanghong; Gazit, Ehud

Supramolecular polymer co-assembly is a useful approach to modulate peptide nanostructures. However, the co-assembly scenario where one of the peptide building blocks simultaneously forms a hydrogel is yet to be studied. Herein, we investigated the co-assembly formation of a minimalistic dipeptide, diphenylalanine (FF), and Fmoc-diphenylalanine (FmocFF) within the 3D fibrous matrix of FmocFF hydrogel. The overlapping peptide sequence between the two building blocks leads to their co-assembly within the gel state modulating the nature of the FF crystals. Consequently, we observe the formation of branched microcrystalline aggregates with an atypical curvature, in contrast to the FF assemblies obtained from aqueous solution. Using optical microscopy, we demonstrate the sigmoidal kinetic growth profile of these aggregates. Microfluidics and ToF-SIMS experiments reveal the presence of co-assembled structures of FF and FmocFF in the crystalline aggregates. Molecular dynamics simulation was further used to decipher the mechanism of co-assembly formation. This study introduces a simple methodology to investigate the kinetics of amyloidogenic structure formation in the hydrogel state and their in vitro modulation using the supramolecular co-assembly paradigm.