Unveiling the Assembly Transition of Diphenylalanine and Its Analogs: from Oligomer Equilibrium to Nanocluster Formation
Year: 2025
Type: article
Abstract: Peptide self-assembly is fundamental to various biological processes and holds significant potential for nanotechnology and biomedical applications. Despite progress in understanding larger-scale assemblies, the early formation of low-molecular-weight oligomers remains poorly understood. In this study, we investigate the aggregation behavior of the self-assembling diphenylalanine (FF) peptide and its analogs. Utilizing single-nanopore analysis, we detected and characterized the low-molecular-oligomer formation of FF, N - tert -butoxycarbonyl-diphenylalanine (BocFF), fluorenylmethyloxycarbonyl-diphenylalanine (FmocFF), and fluorenylmethyloxycarbonyl-pentafluoro-phenylalanine (Fmoc-F 5 -Phe) in real time. This approach provided detailed insights into the early stages of peptide self-assembly, revealing the dynamic behavior and formation kinetics of low-molecular-weight oligomeric species. Analysis revealed that the trimer is the key nucleus for FF, while the dimer is the primary nucleus for FmocFF and Fmoc-F 5 -Phe aggregation, whereas both the dimer and trimer serve as nuclei for BocFF. Mass photometry was employed to track the evolution of these oligomers, revealing the transition from low- to high-molecular-weight species, thereby elucidating intermediate phases in the aggregation process. Transmission electron microscopy and Fourier transform infrared spectroscopy were further employed to characterize the final assembly states, offering high-resolution imaging of morphological structures and detailed information on secondary structures. Based on these analyses, we constructed a comprehensive graph that correlates the entire aggregation processes of the tested self-assembling peptides across multiple scales. This integrative approach provides a holistic understanding of peptide self-assembly, particularly in the formation of low-molecular-weight oligomers toward mature supramolecular structures. These findings shed light on their assembly pathways and structural properties, advancing our understanding of their assembly pathways for nanotechnology and biomedical applications.
Source: ACS Nano
Authors: Chang Liu, Yoav Dan, Ji Yun, Lihi Adler-Abramovich, Jinghui Luo
Institutions: Paul Scherrer Institute, Tel Aviv University, University of Bern
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
Awards: Effects of molecular glues on amyloid protein oligomerization and assembly for potential chemical degradation in the cellular machinery, Structure determination of amyloid oligomer displayed on a functionally and structurally relevant scaffold, Multifunctional Personalized Self-Assembled Biomaterials for Bone Regeneration, G6108673378, G79902365, Structure determination of Alzheimer and Parkinson associated oligomers in lipidic cubic phase
OpenAlex ID: W4408841908