A Comprehensive Landscape for Fibril Association Behaviors Encoded Synergistically by Saccharides and Peptides

Area of Science:

• Supramolecular chemistry
• Materials science
• Biomaterials engineering

Background:

• Nature exhibits diverse fibril structures with complex self-assembly behaviors.
• Creating artificial systems that mimic this complexity, particularly controlling macroscopic properties from molecular building blocks, remains challenging.

Purpose of the Study:

• To develop a method for molecularly encoding fibril association and controlling polymorphism.
• To elucidate the relationship between molecular structure, fibril assembly, and macroscopic properties.

Main Methods:

• Design and synthesis of specific glycopeptide building blocks.
• Utilizing a combination of experimental techniques and computational modeling.
• Characterization of fibril polymorphism, from molecular packing to higher-order assembly.

Main Results:

• A library of controlled fibril polymorphs was generated, exhibiting axial or radial growth with tunable twisting (right- or left-handed).
• The specific balance of oligosaccharide and oligopeptide components dictates fibril growth direction and handedness.
• Experimental and theoretical evidence demonstrated the association process of double-strand fibrils.
• Generated fibril polymorphs exhibited distinct macroscopic properties, including hydrogel formation and cellular migration control.

Conclusions:

• The study successfully demonstrates molecular control over fibril polymorphism and assembly through designed glycopeptide building blocks.
• This work provides a pathway to engineer complex fibril structures with predictable macroscopic functions.
• The findings have implications for designing advanced biomaterials and understanding biological self-assembly processes.