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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.

Photochemical ligation strategies in hydrogel materials are crucial to model spatiotemporal phenomena that occur in the natural extracellular matrix. We here describe the use of cyclic 1,2-dithiolanes to cross-link with norbornene on linear poly(ethylene glycol) polymers through UV irradiation in a rapid and byproduct-free manner, resulting in branched macromolecular architectures and hydrogel materials from low-viscosity precursor solutions. Oscillatory rheology and NMR data indicate the one-pot formation of thioether and disulfide cross-links. Spatial and temporal control of the hydrogel mechanical properties and functionality was demonstrated by oscillatory rheology and confocal microscopy. A cytocompatible response of NIH 3T3 fibroblasts was observed within these materials, providing a foothold for further exploration of this photoactive cross-linking moiety in the biomedical field.

Nucleic acid-polymer conjugates are an attractive class of materials endowed with tunable and responsive character. Herein, we exploit the dynamic character of nucleic acids in the preparation of hybrid DNA-covalent polymers with extendable grafts by the hybridization chain reaction. Addition of DNA hairpins to an initiator DNA-dextran graft copolymer resulted in the growth of the DNA grafts as evidenced by various characterization techniques over several length scales. Additionally, aggregation of the initiator DNA-graft copolymer before the hybridization chain reaction was observed resulting in the formation of kinetically trapped aggregates several hundreds of nanometers in diameter that could be disrupted by a preheating step at 60 °C prior to extension at room temperature. Materials of increasing viscosity were rapidly formed when metastable DNA hairpins were added to the initiator DNA-dextran grafted copolymer with increasing concentration of the components in the mixture. This study shows the potential for hierarchical self-assembly of DNA-grafted polymers through the hybridization chain reaction and opens the door for biomedical applications where viscosity can be used as a readout., Competing Interests: The authors declare no competing financial interest.