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

Abstract

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.

Novel In Situ-Cross-Linked Electrospun Gelatin/Hydroxyapatite Nonwoven Scaffolds Prove Suitable for Periodontal Tissue Engineering

“…Interestingly, the stiffness of a biomaterial can provide all of the necessary biological information to induce proliferation and differentiation of certain cell types. Similar materials are often designated as "cell-instructive" [122,123]. In the periodontal context, this is best exemplified by epitheliogenesis of the gingival epithelium.…”

Dynamic Phosphorus: Thiolate Exchange Cascades with Higher Phosphorothioates

“…Dynamic covalent exchange cascades [1] are emerging as a central process not only to access modern materials [2–15] but also for use in chemical biology, particularly to penetrate cells [16–36] . Exchange cascades operate with dynamic covalent exchangers, which, upon exchange, either produce a new covalently tethered exchanger or offer another exchanger, and thereby continue to exchange.…”

Dynamic Phosphorus: Thiolate Exchange Cascades with Higher Phosphorothioates

“…Dynamic covalent exchange cascades [1] are emerging as a central process not only to access modern materials [2–15] but also for use in chemical biology, particularly to penetrate cells [16–36] . Exchange cascades operate with dynamic covalent exchangers, which, upon exchange, either produce a new covalently tethered exchanger or offer another exchanger, and thereby continue to exchange.…”