pH-Responsive Biocompatible Supramolecular Peptide Hydrogel

Abstract

Peptide-based hydrogels are highly promising for various biomedical applications owing to their precise self-assembly, biocompatibility, and sensitivity toward biologically relevant external stimuli. Herein, we report pH-responsive self-assembly and gelation of a highly biocompatible amphiphilic peptide PEP-1. This is an octa-peptide and double mutant of a naturally occurring β-strand peptide fragment of the protein Galectin-1, available in bovine spleen. PEP-1 was synthesized by using the Rink amide resin as the solid support in a homemade apparatus. At pH 7.4, it exhibits spontaneous gelation with very high yield stress of 88.0 Pa and gel-to-sol temperature of 84 °C at C = 2.0 wt %. Microscopy studies revealed entangled fibrillar morphology whereas circular dichroism, Fourier tranform IR, and Thioflavin T assay indicated formation of β-sheet rich secondary structure. The assembled state was found to be stable in neutral pH whereas either decrease or increase in the pH resulted in disassembly owing to the presence of the pH responsive Asp and Lys residues. The gel network showed ability to entrap water-soluble guest molecules such as Calcein which could be selectively released at acidic pH whereas under neutral condition the release was negligible. MTT assay revealed remarkable biocompatibility of the PEP-1 gel as almost 100% cells were alive after 48 h incubation in the presence of PEP-1 (2.0 mg/mL).