Shear-Thinning and Rapid-Recovery Peptide Hydrogel for Biomedical Applications
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Shear-Thinning and Rapid-Recovery Peptide Hydrogel for Biomedical Applications Hongzhou John Huang1 and Xiuzhi Susan Sun1* 1
Biomaterial and Technology Laboratory, Department of Grain Science and Industry, Kansas State University, 1980 Kimball Avenue, Manhattan, KS 66506, U.S.A. *Corresponding author ABSTRACT Peptides have become attractive molecules for fabricating biomaterials. Studies of peptide structure, assembly properties, and dynamic behavior in response to external parameters have led to rational novel design of peptide biomaterials. One model sequence selected was a ȕspiral motif of spider flagelliform silk protein, [GPGGX]n (X = any amino acid). Modifying the X residue can change the quantity of secondary structure and the stability of this spider silk motif. Glycine provides flexible properties, and proline influences the secondary structure and mechanical properties. Another model sequence was GXGXDXUX (U = hydrophobic residue), a Ca2+ binding domain of lipase Lip A from Serratia marcescens, in which aspartate residue is required for ion binding. Combining with [GPGGX]n, we rationally designed peptide as GPGGDGPGGD (eD2). The Ca2+ binding sequence was hidden in the first eight residues of eD2. As expected, this peptide can assemble into nanofibrils triggered by Ca2+ ions. Using the segment FLIVIGSII (h9) from the third trans-membrane segment of subunit IV in the dihydropyridine sensitive human muscle L-type calcium channel as the hydrophobic motif, we obtained FLIVIGSIIGPGGDGPGGD (h9e) peptide. The h9e self-assembled into nanofibrils and further formed shear-thinning and rapid recovery hydrogel in neutral pH range from 6.0 to 8.0 with a large working range of temperature. NMR study showed that amphiphilic structure of h9e peptide tended to adopt a more helical structure during hydrogel formation. The h9e peptide has great potential for biomedical applications. MCF-7 cells were successfully grown as colony-like clusters (reminiscent of real tumors) in h9e hydrogel system. The drug response test of cisplatin further demonstrated the capability of h9e system for drug screen. Moreover, h9e hydrogel showed a promising adjuvanticity by enhancing the vaccine efficacy for killed H1N1 swine influenza virus and PRRS modified live virus. INTRODUCTION The process of self-assembly is reflected to an aggregated pathway of molecular spontaneous organization which is observed in many natural phenomenon such as cell membrane formation, protein-protein interaction, DNA expression and so on [1-5]. Studying molecular selfassembly is not only critical to understanding the biological functions of a wide range of biomolecules and mechanism of many human diseases, but also inspires material scientists to design and synthesize building blocks in molecular level with capability to self-assemble into well-ordered nanostructures for developing new functional biomaterials [6-8]. Peptide is a short sequence of amino acids linked through peptide bonds. According to the side chain of each amino acid residue, peptides have amphiphilic
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