Lopez-Silva Tania L, Leach David G, Li I-Che, Wang Xinran, Hartgerink Jeffrey D
Department of Chemistry, Rice University, Houston, Texas 77005, United States.
Department of Bioengineering, Rice University, Houston, Texas 77005, United States.
ACS Biomater Sci Eng. 2019 Feb 11;5(2):977-985. doi: 10.1021/acsbiomaterials.8b01348. Epub 2018 Dec 20.
Self-assembly of peptides is a powerful method of preparing nanostructured materials. These peptides frequently utilize charged groups as a convenient switch for controlling self-assembly in which pH or ionic strength determines the assembly state. Multidomain peptides have been previously designed with charged domains of amino acids, which create molecular frustration between electrostatic repulsion and a combination of supramolecular forces including hydrogen bonding and hydrophobic packing. This frustration is eliminated by the addition of multivalent ions or pH adjustment, resulting in a self-assembled hydrogel. However, these charged functionalities can have profound, unintended effects on the properties of the resulting material. Access to neutral self-assembled nanostructured hydrogels may allow for distinct biological properties that are not available to highly charged analogues. Here, we designed a series of peptides to determine if self-assembly could be mediated by the steric interactions created by neutral hydroxyproline (O) domains, eliminating the need for charged residues and creating a neutral peptide hydrogel. The series of peptides, O (SL)O , was studied to determine the effect of oligo-hydroxyproline on peptide self-assembly and nanostructure. We show that peptide solubility and nanofiber length increase with a higher number of hydroxyproline residues. Within this series, O(SL)O displayed the optimal properties for self-assembly and hydrogelation. In vitro, this hydrogel supports cell viability of fibroblasts, while in vivo it is infiltrated with cells and easily degraded over time without promoting a strong inflammatory response. This neutral self-assembling peptide hydrogel shows promising properties for biomedical, cell preservation, and tissue regeneration applications.
肽的自组装是制备纳米结构材料的一种有效方法。这些肽经常利用带电基团作为控制自组装的便捷开关，其中pH值或离子强度决定组装状态。此前已设计出具有氨基酸带电结构域的多结构域肽，这些结构域在静电排斥与包括氢键和疏水堆积在内的超分子力组合之间产生分子受挫现象。通过添加多价离子或调节pH值可消除这种受挫现象，从而形成自组装水凝胶。然而，这些带电官能团可能会对所得材料的性能产生深远的意外影响。获得中性自组装纳米结构水凝胶可能会带来高度带电类似物所不具备的独特生物学特性。在此，我们设计了一系列肽，以确定自组装是否可以由中性羟脯氨酸（O）结构域产生的空间相互作用介导，从而无需带电残基并形成中性肽水凝胶。对该系列肽O（SL）O进行了研究，以确定寡聚羟脯氨酸对肽自组装和纳米结构的影响。我们发现，随着羟脯氨酸残基数量的增加，肽的溶解度和纳米纤维长度会增加。在该系列中，O（SL）O展现出自组装和水凝胶化的最佳性能。在体外，这种水凝胶支持成纤维细胞的细胞活力，而在体内，它会被细胞浸润并随着时间的推移容易降解，且不会引发强烈的炎症反应。这种中性自组装肽水凝胶在生物医学、细胞保存和组织再生应用方面显示出良好的性能。
