Dipeptide-based Co-assembly Systems: Molecular Design, Multi-scale Manipulation And Biological Applications

In this work, we are devoted to the study of the self-assembly of short aromatic dipeptides. We fabricated novel self-assembling peptide with multi-stimuli responsiveness and chiral self-assembling behavior, and designed “peptide-peptide” or “biomacromole-peptide” co-assembling systems. Moreover, inspired by the concepts from interfacial physics and chemical engineering, we exploited novel self-assembling manipulation strategies to control the hierarchical co-assembly of peptides into highly ordered and functional peptide materials, which have great potential applications in chiral sensing and bioengineering.(1) Putting metals into organic compound such as peptides can lead to many new desirable properties. We designed a novel bioorganometallic molecule, ferrocene-diphenylalanine(Fc-FF), and investigated its self-assembly behavior. We directly observed a morphological transition from metastable nanospheres to nanofibers, which led to the formation of a self-supporting hydrogel. Moreover, the hydrogel formed by the hierarchical self-assembly of Fc-FF show multi-stimuli responsiveness, and the sol-gel transtion can be reversed by a slight change of pH, temperature, solvent or the redox state of the Fc moiety.(2) We report a new paradigm for the rational design of chiral nanostructures based on the hierarchical self-assembly of a ferrocene(Fc)-modified dipeptide, ferrocene-L-Phe-L-Phe-OH(Fc-FF). X-ray and spectroscopic analyses showed that the incorporation of counterions during the hierarchical self-assembly of Fc-FF changed the conformations of the secondary structures from flat β-sheets into twisted β-sheets. This approach enables chiral self-assembly and the formation of well-defined chiral nanostructures composed of helical twisted β-sheets. Furthermore, through subtle modulations in the counterions, temperature and solvent, we are able to precisely control the helical pitch, diameter and handedness of the self-assembled chiral nanostructures. This unprecedented level of control not only offers insights into how rationally designed chiral nanostructures can be formed from simple molecular building blocks but is also of significant practical value for the use in chiroptics, templates, chiral sensing and separations.(3) “Coffee ring” effect is ubiquitous in nature, the capillary force underlying this phenomenon can be used to control the hierarhically chiral self-assembly of Fc-FF into well-defined nanohelices. Through altering the temperature, we can control the strengh of marangoni flow within an evaporating drops and modulate the balance between the capillary flow and the maragoni flow. This allows us to control the directed growth of Fc-FF nanohelices into horizontal or vertial aligned nanohelic arrays after the solvent is fully evaporated.(4) The wetting and drying of drops on flexible fibers occurs ubiquitously in nature, and the capillary force underlying this phenomenon has motivated our great interest in learning how to direct supramolecular self-assembly. We demonstrate that dandelion-like peptide microstructure can be formed via the sequential, combinatorial co-assembly of diphenylalanine(FF) and ferrocene-diphenylalanine(Fc-FF). This microstructure has highly complex architectures, where FF microtube arrays serve as the scapes and the Fc-FF nanofibers serve as the flower heads. The capillary force derived from the wetting and drying process is crucial for the formation of such complex peptide microstructure.(5) We demonstrated the formation of lamellar hydrogels to robust membranes and sacs through the hierarchical self-assembly of aromatic dipeptides and polysaccharide chitosan. The self-assembly was achieved at an aqueous liquid-liquid interface between the dipeptide and chitosan solutions. The resulting lamellar hydrogel shows the features of liquid crystals and contains macroscopically layered domains at the scale up to centimeters. While the membranes and sacs exhibit high mechanical strength, tunable permeability and pH-responsiveness, and have good performance for controlled release. In comparison to other self-assembling peptides, the aromatic dipeptides are much smaller and easier to be synthesized(low cost). The self-assembly of these dipeptides with functional polysaccharide chitosan will have practical applications in many areas, including serving as biocompatible scaffolds to direct the long-range alignment of cells, large-scale manufacture of microcapsules for controlled drug release, and enzyme immobilization.(6) We demonstrated a jet flow directed supramolecular self-assembly at the interface between two aqueous solutions, one containing a cationic polyacrylamide(CPAM) and the other, small self-assembling Fmoc-diphenylalanine(Fmoc-FF) peptide bearing opposite charge. By controlling the jet flow of CPAM solution, we can fabricate macroscopic sac membranes, or microfibers composed of well-aligned Fmoc-FF nanofibers at the interface between two solutions. Moreover, the structure of microfibers may be hollow or solid depending on the intensity of jet flow. The entrainment of the jet flow will enhance the mixing between Fmoc-FF and CPAM solutions, which can be utilized for the fast fabrication of well-defined Fmoc-FF/CPAM microfibers. These microfibers can encapsulate functional components facilely for controlled drug release.