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Tuning Gelation Kinetics and Mechanical Rigidity of β‑Hairpin Peptide Hydrogels via Hydrophobic Amino Acid Substitutions
journal contributionposted on 2014-08-27, 00:00 authored by Cuixia Chen, Yanfeng Gu, Li Deng, Shuyi Han, Xing Sun, Yucan Chen, Jian R. Lu, Hai Xu
Self-assembling peptide hydrogels with faster gelation kinetics and higher mechanical rigidity are favorable for their practical applications. A design strategy to control the folding, self-assembly, and hydrogelation of β-hairpin peptides via hydrophobic amino acid substitutions has been explored in this study. Isoleucine has higher hydrophobicity and stronger propensity for β-sheet hydrogen bonding than valine. After the valine residues of MAX1 (VKVKVKVKVDPPTKVKVKVKV-NH2) were replaced with isoleucines, oscillatory rheometry and circular dichroism (CD) spectroscopy characterizations indicated that the variants had clearly faster self-assembly and hydrogelation rates and that the resulting gels displayed higher mechanical stiffness. Transmission electron microscopy (TEM) indicated the parent MAX1 and its variants all formed networks of long and entangled fibrils with the similar diameters of ∼3 nm, suggesting little effect of hydrophobic substitutions on the self-assembled morphology. The MAX1I8 (IKIKIKIKVDPPTKIKIKIKI-NH2) hydrogel showed the fastest gelation rate (within 5 min) and the highest gel rigidity with the series, supporting the homogeneous cell distribution within its 3D scaffold. In addition, the MAX1I8 hydrogel showed quick shear-thinning and rapid recovery upon cessation of shear strain, and the MTT and immunological assays indicated its low cytotoxicity and good biocompatibility. These features are highly attractive for its widespread use in 3D cell culturing and regenerative medical treatments.
MAX 1I hydrogelparent MAX 1transmission electron microscopy5 minpeptideMAX 1ITuning Gelation Kinetics3 D scaffold3 D cell culturingMAX 1shear straincell distributionvaline residuesMechanical RigidityVKVKHydrophobic AminoTEMdesign strategygelation kineticshydrogelation ratesspectroscopy characterizationsgel rigidityIKIKacid substitutionsgelation rateoscillatory rheometryvariantMTT