Controlling supramolecular filament chirality of hydrogel by co-assembly of enantiomeric aromatic peptides

Abstract

Supramolecular chirality plays an indispensable role in living and synthetic systems. However, the generation and control of filament chirality in the supramolecular hydrogel of short peptides remains challenging. In this work, as the first example, we report that the heterodimerization of the enantiomeric mixture controls the alignment, chirality, and stiffness of fibrous hydrogels formed by aromatic building blocks. The properties of the resulting racemic hydrogel could not be achieved by either pure enantiomer. Cryo-EM images indicate that the mixture of L and D enantiomers forms chiral nanofibers, the percentage of which can be readily controlled through stoichiometric co-assembly of heterochiral enantiomers. 2D NOESY NMR and diffusion-ordered NMR spectroscopy reveal that heterodimerization of enantiomers plays a crucial role in the formation of chiral nanofibers. Further mechanistic studies unravel the mechanism of supramolecular chirality formation in this two-component system. Molecular dynamics simulations confirm that the intermolecular hydrogen bond and π–π interaction of heterodimers play important roles in forming a chiral hydrogel. Furthermore, regulation of the adhesion and morphology of mammalian cells is achieved by tuning the relative ratio of L and D enantiomers at the same concentration. This work illustrates a novel strategy to control the supramolecular chirality of aromatic peptide hydrogels for materials science. Graphical Abstract

A Dual-Responsive Peptide Hydrogel Protects Normal Cells from Anticancer Drug Treatments

“…The CD spectra showed that 1p (150 μM) adopted a random coil structure (Figure B). In contrast, upon addition of ALP (2 U μL –1 ), the resulting 1 exhibited a β-sheet-like secondary structure, as evidenced by the presence a negative peak at 233 nm …”

“…In contrast, upon addition of ALP (2 U μL −1 ), the resulting 1 exhibited a β-sheet-like secondary structure, as evidenced by the presence a negative peak at 233 nm. 37 To evaluate the gelation properties of 1p, we initial mixed 1p with 2 × HEPES buffer (50 mM HEPES, 300 mM NaCl, pH 7.4). Initially, 1p formed only a clear solution, with no detectable fibers present.…”

Mechanisms and influencing factors of peptide hydrogel formation and biomedicine applications of hydrogels

“…For example, amino acids in the l -configuration can form α-helices, β-sheets or disordered structures through hydrogen bonds or π–π stacking interactions. 79,80…”

“…For example, amino acids in the L-configuration can form a-helices, b-sheets or disordered structures through hydrogen bonds or p-p stacking interactions. 79,80 Kang et al 81 designed hydrogels L-Ala-co-L-Phe and D-Ala-co-D-Phe containing amino acid residues in different configurations. These two polymers have similar molecular weights, sol-gel transition behaviors and mirror a-helix structures but have significantly different hydrogel degradation behaviors.…”

The Role of Functional Groups in Tuning the Self‐Assembly Modes and Physical Properties of Multicomponent Gels

“…Mixing enantiomeric gels can induce self‐recognition at the molecular level due to the structural similarity of individual components resulting in gels with better packing and favorable properties [4] that are not accessed by individual enantiomeric gels. Multicomponent systems based on enantiomeric compounds tend to favor co‐assembly over self‐sorting, [4a–n] but self‐sorted fibers are obtained if the components with identical conformation display favorable interaction [4o–r] leading to conglomerates (Scheme 1).…”