Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, School of Science, Westlake University, Hangzhou, China.
Institute of Natural Sciences, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou, 310024, Zhejiang Province, China.
J Nanobiotechnology. 2022 Feb 10;20(1):77. doi: 10.1186/s12951-022-01285-0.
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.
超分子手性在生命和合成体系中起着不可或缺的作用。然而,短肽的超分子水凝胶中纤维手性的产生和控制仍然具有挑战性。在这项工作中,作为第一个例子,我们报告说,手性混合物的杂二聚体控制了由芳香族构建块形成的纤维水凝胶的排列、手性和刚性。通过纯对映体无法实现所得外消旋水凝胶的性质。低温电子显微镜图像表明,L 和 D 对映异构体的混合物形成手性纳米纤维,其比例可以通过异手性对映异构体的化学计量共组装轻松控制。2D NOESY NMR 和扩散有序 NMR 光谱揭示了对映异构体的杂二聚化在手性纳米纤维形成中起着关键作用。进一步的机理研究阐明了这种两成分体系中超分子手性形成的机理。分子动力学模拟证实了杂二聚体的分子间氢键和π-π相互作用在手性水凝胶形成中起着重要作用。此外,通过在相同浓度下调节 L 和 D 对映异构体的相对比例,可以实现哺乳动物细胞的粘附和形态的调节。这项工作说明了一种控制芳香族肽水凝胶的超分子手性的新策略,用于材料科学。