Supramolecular Click Product Interactions Induce Dynamic Stiffening of Extracellular Matrix-Mimetic Hydrogels.

Progressive stiffening of the extracellular matrix (ECM) is observed in tissue development as well as in pathologies such as cancer, cardiovascular disease, and fibrotic disease. However, methods to recapitulate this phenomenon face critical limitations. Here, we present a poly(ethylene glycol)-based peptide-functionalized ECM-mimetic hydrogel platform capable of facile, user-controlled dynamic stiffening.

Hydrogel Synthesis and Stabilization via Tetrazine Click-Induced Secondary Interactions.

The discovery of tetrazine click-induced secondary interactions is reported as a promising new tool for polymeric biomaterial synthesis. This phenomenon is first demonstrated as a tool for poly(ethylene glycol) (PEG) hydrogel assembly via purely non-covalent interactions and is shown to yield robust gels with storage moduli one to two orders of magnitude higher than other non-covalent crosslinking methods. In addition, tetrazine click-induced secondary interactions also enhance the properties of covalently crosslinked hydrogels.

β-Catenin maintains lung epithelial progenitors after lung specification.

The entire lung epithelium arises from SRY box 9 (SOX9)-expressing progenitors that form the respiratory tree and differentiate into airway and alveolar cells. Despite progress in understanding their initial specification within the embryonic foregut, how these progenitors are subsequently maintained is less clear. Using inducible, progenitor-specific genetic mosaic mouse models, we showed that β-catenin (CTNNB1) maintains lung progenitors by promoting a hierarchical lung progenitor gene signature, suppressing gastrointestinal (GI) genes, and regulating NK2 homeobox 1 (NKX2.