Fluorescein-based SynNotch adaptors for regulating gene expression responses to diverse extracellular and matrix-based cues.

ABSTRACT: Synthetic Notch (SynNotch) receptors function like natural Notch proteins and can be used to install customized sense-and-respond capabilities into mammalian cells. Here, we introduce an adaptor-based strategy for regulating SynNotch activity via fluorescein isomers and analogs. Using an optimized fluorescein-binding SynNotch receptor, we describe ways to chemically control SynNotch signaling, including an approach based on a bio-orthogonal chemical ligation and a spatially controllable strategy via the photo-patterned uncaging of an o-nitrobenzyl-caged fluorescein conjugate. We further show that fluorescein-conjugated extracellular matrix (ECM)-binding peptides can be used to regulate SynNotch activity depending on the folding state of collagen-based ECM networks. To demonstrate the utili

SUBMITTER: Tran JC 

PROVIDER: S-EPMC11756391 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature