Urea-Modified Self-Assembling Peptide Amphiphiles That Form Well-Defined Nanostructures and Hydrogels for Biomedical Applications
Urea-Modified Self-Assembling Peptide Amphiphiles That Form Well-Defined Nanostructures and Hydrogels for Biomedical Applications
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DOI：
10.1021/acsabm.2c00158
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发表时间：
2022-06-02
影响因子：
4.7
通讯作者：
Conda-Sheridan，Martin
中科院分区：
文献类型：
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作者：
Xing，Huihua;Rodger，Alison;Conda-Sheridan，Martin
氢键在肽两亲物（PAs）的自组装过程中起着至关重要的作用。在本文中，我们研究了用脲基取代PA的肽和脂质部分之间的酰胺键的效果，所述脲基具有额外的氢键供体。我们制备了三个具有肽序列Phe-Phe-Glu-Glu（FFEE）的PA：两个是与不同长度的疏水尾部酰胺连接的，另一个具有烷基化脲基团。使用不同的显微镜，核磁共振（NMR），和二色性技术，这些PA形成的自组装结构的差异进行了评估。我们发现，脲基团的影响的形态和内部排列的组装。分子动力学模拟表明，有大约50%以上的氢键在纳米结构组装从尿素PA比组装从其他PA。此外，计算机模拟研究表明，与Phe的苯基基团存在脲-π堆积相互作用，这导致与酰胺连接的PA相比不同的肽构象。然后，我们研究了尿素改性对PA水凝胶的力学性能的影响。我们发现由尿素-PA制成的水凝胶表现出增加的稳定性和自修复能力。此外，它允许细胞粘附、扩散和作为基质生长。这项研究表明，包括脲键可能是有用的，在控制的形态，机械和生物学性能的自组装纳米结构和水凝胶形成的PA。
Hydrogen bonding plays a critical role in the self-assembly of peptide amphiphiles (PAs). Herein, we studied the effect of replacing the amide linkage between the peptide and lipid portions of the PA with a urea group, which possesses an additional hydrogen bond donor. We prepared three PAs with the peptide sequence Phe-Phe-Glu-Glu (FFEE): two are amide-linked with hydrophobic tails of different lengths and the other possesses an alkylated urea group. The differences in the self-assembled structures formed by these PAs were assessed using diverse microscopies, nuclear magnetic resonance (NMR), and dichroism techniques. We found that the urea group influences the morphology and internal arrangement of the assemblies. Molecular dynamics simulations suggest that there are about 50% more hydrogen bonds in nanostructures assembled from the urea-PA than those assembled from the other PAs. Furthermore,in silicostudies suggest the presence of urea−π stacking interactions with the phenyl group of Phe, which results in distinct peptide conformations in comparison to the amide-linked PAs. We then studied the effect of the urea modification on the mechanical properties of PA hydrogels. We found that the hydrogel made of the urea-PA exhibits increased stability and self-healing ability. In addition, it allows cell adhesion, spreading, and growth as a matrix. This study reveals that the inclusion of urea bonds might be useful in controlling the morphology, mechanical, and biological properties of self-assembled nanostructures and hydrogels formed by the PAs.