A Supramolecular Platform for the Introduction of Fc-Fusion Bioactive Proteins on Biomaterial Surfaces.

ABSTRACT: Bioorthogonal chemistry is an excellent method for functionalization of biomaterials with bioactive molecules, as it allows for decoupling of material processing and bioactivation. Here, we report on a modular system created by means of tetrazine/trans-cyclooctene (Tz/TCO) click chemistry undergoing an inverse electron demand Diels-Alder cycloaddition. A reactive supramolecular surface based on ureido-pyrimidinones (UPy) is generated via a UPy-Tz additive, in order to introduce a versatile TCO-protein G conjugate for immobilization of Fc-fusion proteins. As a model bioactive protein, we introduced Fc-Jagged1, a Notch ligand, to induce Notch signaling activity on the material. Interestingly, HEK293 FLN1 cells expressing the Notch1 receptor were repelled by films modified with TCO-protein G but adhered and spread on functionalized electrospun meshes. This indicates that the material processing method influences the biocompatibility of the postmodification. Notch signaling activity was upregulated 5.6-fold with respect to inactive controls on electrospun materials modified with TCO-protein G/Fc-Jagged1. Furthermore, downstream effects of Notch signaling were detected on the gene level in vascular smooth muscle cells expressing the Notch3 receptor. Taken together, our results demonstrate the successful use of a modular supramolecular system for the postprocessing modification of solid materials with functional proteins.

SUBMITTER: Putti M 

PROVIDER: S-EPMC6691680 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature