Spatial and Temporal Modulation of Cell Instructive Cues in a Filamentous Supramolecular Biomaterial

• DOI: 10.1021/acsami.1c24114
• Publication Date: 2022-04-10T14:50:40Z
• Authors: Ciqing Tong; Joeri A. J. Wonde...; Marijn van den Brink; Markus C. Kwakernaak; Ying Chen; Marco M. R. M. He...; Ilja K. Voets; Erik H. J. Danen; Sylvia Le Dévédec; Doris Heinrich; Roxanne E. Kieltyka
• Keywords: 3D cell culture; photopatterning; Cell Culture Techniques; Biocompatible Materials; Hydrogels; Photopatterning; 3D Cell Culture; 01 natural sciences; Dithiolane; Extracellular Matrix; 0104 chemical sciences; Cues; Aupramolecular; dithiolane; hydrogels; supramolecular

Supramolecular materials provide unique opportunities to mimic both the structure and mechanics of the biopolymer networks that compose the extracellular matrix. However, strategies to modify their filamentous structures in space and time in 3D cell culture to study cell behavior as encountered in development and disease are lacking. We herein disclose a multicomponent squaramide-based supramolecular material whose mechanics and bioactivity can be controlled by light through co-assembly of a 1,2-dithiolane (DT) monomer that forms disulfide cross-links. Remarkably, increases in storage modulus from ∼200 Pa to >10 kPa after stepwise photo-cross-linking can be realized without an initiator while retaining colorlessness and clarity. Moreover, viscoelasticity and plasticity of the supramolecular networks decrease upon photo-irradiation, reducing cellular protrusion formation and motility when performed at the onset of cell culture. When applied during 3D cell culture, force-mediated manipulation is impeded and cells move primarily along earlier formed channels in the materials. Additionally, we show photopatterning of peptide cues in 3D using either a photomask or direct laser writing. We demonstrate that these squaramide-based filamentous materials can be applied to the development of synthetic and biomimetic 3D in vitro cell and disease models, where their secondary cross-linking enables mechanical heterogeneity and shaping at multiple length scales.