Molecular dynamics study and preparation of aligned fibrin hydrogel grafted with RADA16-based functional peptide

• Published in: Macromolecular research 2023, 31(7), , pp.649-662
• Main Authors: Yao, Shenglian, Fa, Xinying, Chen, Ruomeng, Wang, Xiumei, Wang, Luning
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Biological activity; Biological products; Biomedical materials; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Complex Fluids and Microfluidics; Complex systems; Electron microscopy; Fibrin; Hydrogels; Hydrophobicity; Microscopy; Molecular dynamics; Nanochemistry; Nanotechnology; Peptides; Physical Chemistry; Polymer Sciences; Regeneration (physiology); Soft and Granular Matter; Static electricity; Structural analysis; Tissue engineering; Van der Waals forces; 고분자공학
• ISSN: 1598-5032; 2092-7673
• DOI: 10.1007/s13233-023-00159-0

Bioactive scaffold design is always a key factor for neural tissue engineering, and decides the results of neural tissue regeneration. Fibrin hydrogel and RADA16-based functional peptides, as two kinds of soft hydrogel biomaterials, were successfully designed and used for neural tissue engineering. In this work, the interaction of fibrin and RADA16-based functional peptide was examined through a molecular dynamics study, and the results could be used to identify whether the combination of the two kinds of hydrogel is realizable and effective. In this study, RADA16-conjugated neurotrophic peptide (RAD-RGI) was developed by grafting neurotrophic peptide RGI (RGIDKRHWNSQ) to the C-terminus of amphiphilic peptide RADA16-I (Ac-(RADA) 4 -CONH 2 ). The molecular dynamics simulations results indicated that RAD-RGI bound to fibrin autonomously and distributed randomly mostly under the action of intermolecular static electricity, van der Waals force, and hydrophobicity as well. In addition, the positive charged and non-polar residues play crucial roles in peptide-fibrin interactions. From the structural analysis result of the peptide with the highest content of α-helix structure in the composite system, RAD-RGI was bound to fibrin with amino acids in the region of RADA, while RGI motifs maintained its original structure and function in the binding process that provided the fibrin composite hydrogel with neurotrophic bioactivity. Finally, the RAD-RGI/aligned fibrin hydrogel (RAD-RGI/AFG) was successfully fabricated, and the composite hydrogel’s microstructure was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). This research provides theoretical support for the combination of fibrin hydrogel with RADA16-conjugated neurotrophic peptides in the design of neural tissue engineering biomaterials. Graphical abstract The Illustration of the RAD-RGI/AFG hydrogel formation and the 3D interaction map of RAD-RGI peptide with the lowestfree energy and AFG for the RAD-RGI/AFG complex system