A supramolecular platform for the introduction of Fc-fusion bioactive proteins on biomaterial surfaces

Research output: Contribution to journalArticleAcademicpeer-review

10 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)2044-2054
Number of pages11
JournalACS Applied Polymer Materials
Volume1
Issue number8
DOIs
Publication statusPublished - 9 Aug 2019

Fingerprint

Biocompatible Materials
Pyrimidinones
Proteins
Notch1 Receptor
Click Chemistry
HEK293 Cells
Cycloaddition Reaction
Vascular Smooth Muscle
Immobilization
Smooth Muscle Myocytes
Electrons
Ligands
Genes

Cite this

@article{ca6c682226ed42658808c3c55c14b282,
title = "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.",
author = "Sahlgren, {Cecilia M.} and {de Jong}, {Simone M.J.} and Stassen, {Oscar M.J.A.} and Sahlgren, {Cecilia M.} and Dankers, {Patricia Y.W.}",
year = "2019",
month = "8",
day = "9",
doi = "10.1021/acsapm.9b00334",
language = "English",
volume = "1",
pages = "2044--2054",
journal = "ACS Applied Polymer Materials",
issn = "2637-6105",
publisher = "American Chemical Society",
number = "8",

}

TY - JOUR

T1 - A supramolecular platform for the introduction of Fc-fusion bioactive proteins on biomaterial surfaces

AU - Sahlgren, Cecilia M.

AU - de Jong, Simone M.J.

AU - Stassen, Oscar M.J.A.

AU - Sahlgren, Cecilia M.

AU - Dankers, Patricia Y.W.

PY - 2019/8/9

Y1 - 2019/8/9

N2 - 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.

AB - 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.

U2 - 10.1021/acsapm.9b00334

DO - 10.1021/acsapm.9b00334

M3 - Article

C2 - 31423488

VL - 1

SP - 2044

EP - 2054

JO - ACS Applied Polymer Materials

JF - ACS Applied Polymer Materials

SN - 2637-6105

IS - 8

ER -