Luciferin-Bioinspired Click Ligation Enables Hydrogel Platforms with Fine-Tunable Properties for 3D Cell Culture

Minye Jin, Gülistan Koçer, Julieta I. Paez*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
8 Downloads (Pure)


There is an increasing interest in coupling reactions for cross-linking of cell-encapsulating hydrogels under biocompatible, chemoselective, and tunable conditions. Inspired by the biosynthesis of luciferins in fireflies, here we exploit the cyanobenzothiazole-cysteine (CBT-Cys) click ligation to develop polyethylene glycol hydrogels as tunable scaffolds for cell encapsulation. Taking advantage of the chemoselectivity and versatility of CBT-Cys ligation, a highly flexible gel platform is reported here. We demonstrate luciferin-inspired hydrogels with important advantages for cell encapsulation applications: (i) gel precursors derived from inexpensive reagents and with good stability in aqueous solution (>4 weeks), (ii) adjustable gel mechanics within physiological ranges (E = 180-6240 Pa), (iii) easy tunability of the gelation rate (seconds to minutes) by external means, (iv) high microscale homogeneity, (v) good cytocompatibility, and (iv) regulable biological properties. These flexible and robust CBT-Cys hydrogels are proved as supportive matrices for 3D culture of different cell types, namely, fibroblasts and human mesenchymal stem cells. Our findings expand the toolkit of click chemistries for the fabrication of tunable biomaterials.

Original languageEnglish
Pages (from-to)5017-5032
Number of pages16
JournalACS Applied Materials and Interfaces
Issue number4
Publication statusPublished - 2 Feb 2022
Externally publishedYes


  • 3D cell encapsulation
  • Bioactivity
  • Bioinspired materials
  • Cyanobenzothiazole-cysteine click ligation
  • Hydrogels
  • Luciferin adduct
  • Tunable gelation rate
  • n/a OA procedure


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