Criado-Gonzalez Miryam, Peñas Mario Iván, Barbault Florent, Müller Alejandro J, Boulmedais Fouzia, Hernández Rebeca
Instituto de Ciencia y Tecnología de Polímeros (ICTP-CSIC), 28006 Madrid, Spain.
POLYMAT and Department of Polymers and Advanced Materials: Physics, Chemistry and Technology, Faculty of Chemistry, University of the Basque Country UPV/EHU, 20018 Donostia-San Sebastián, Spain.
Nanoscale. 2024 May 23;16(20):9887-9898. doi: 10.1039/d4nr00335g.
Delving into the mechanism behind the molecular interactions at the atomic level of short-sequence peptides plays a key role in the development of nanomaterials with specific structure-property-function relationships from a bottom-up perspective. Due to their poor water solubility, the self-assembly of Fmoc-bearing peptides is usually induced by dissolution in an organic solvent, followed by a dilution step in water, pH changes, and/or a heating-cooling process. Herein, we report a straightforward methodology for the gelation of Fmoc-FFpY (F: phenylalanine; Y: tyrosine; and p: PO), a negatively charged tripeptide, in NaCl solution. The electrostatic interactions between Fmoc-FFpY and Na ions give rise to different nanofibrillar hydrogels with rheological properties and nanofiber sizes modulated by the NaCl concentration in pure aqueous media. Initiated by the electrostatic interactions between the peptide phosphate groups and the Na ions, the peptide self-assembly is stabilized thanks to hydrogen bonds between the peptide backbones and the π-π stacking of aromatic Fmoc and phenyl units. The hydrogels showed self-healing and thermo-responsive properties for potential biomedical applications. Molecular dynamics simulations from systems devoid of prior training not only confirm the aggregation of peptides at a critical salt concentration and the different interactions involved, but also corroborate the secondary structure of the hydrogels at the microsecond timescale. It is worth highlighting the remarkable achievement of reproducing the morphological behavior of the hydrogels using atomistic simulations. To our knowledge, this study is the first to report such a correspondence.
从自下而上的角度深入研究短序列肽在原子水平上的分子相互作用机制，对于开发具有特定结构-性质-功能关系的纳米材料起着关键作用。由于其水溶性差，含Fmoc的肽的自组装通常通过溶解在有机溶剂中，然后在水中进行稀释步骤、pH变化和/或加热-冷却过程来诱导。在此，我们报道了一种在NaCl溶液中使带负电荷的三肽Fmoc-FFpY（F：苯丙氨酸；Y：酪氨酸；p：PO）凝胶化的直接方法。Fmoc-FFpY与Na离子之间的静电相互作用产生了不同的纳米纤维水凝胶，其流变性质和纳米纤维尺寸在纯水性介质中受NaCl浓度调节。由肽磷酸基团与Na离子之间的静电相互作用引发，肽的自组装通过肽主链之间的氢键以及芳香族Fmoc和苯基单元的π-π堆积得以稳定。这些水凝胶表现出自我修复和热响应特性，具有潜在的生物医学应用价值。来自未经预先训练的系统的分子动力学模拟不仅证实了肽在临界盐浓度下的聚集以及所涉及的不同相互作用，还在微秒时间尺度上证实了水凝胶的二级结构。值得强调的是，使用原子模拟再现水凝胶的形态行为取得了显著成果。据我们所知，本研究是首次报道这种对应关系。
