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Synthesis of bioactive protein hydrogels by genetically encoded SpyTag-SpyCatcher chemistry

Sun, Fei and Zhang, Wen-Bin and Mahdavi, Alborz and Arnold, Frances H. and Tirrell, David A. (2014) Synthesis of bioactive protein hydrogels by genetically encoded SpyTag-SpyCatcher chemistry. Proceedings of the National Academy of Sciences of the United States of America, 111 (31). pp. 11269-11274. ISSN 0027-8424. PMCID PMC4128157. doi:10.1073/pnas.1401291111.

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Protein-based hydrogels have emerged as promising alternatives to synthetic hydrogels for biomedical applications, owing to the precise control of structure and function enabled by protein engineering. Nevertheless, strategies for assembling 3D molecular networks that carry the biological information encoded in full-length proteins remain underdeveloped. Here we present a robust protein gelation strategy based on a pair of genetically encoded reactive partners, SpyTag and SpyCatcher, that spontaneously form covalent isopeptide linkages under physiological conditions. The resulting “network of Spies” may be designed to include cell-adhesion ligands, matrix metalloproteinase-1 cleavage sites, and full-length globular proteins [mCherry and leukemia inhibitory factor (LIF)]. The LIF network was used to encapsulate mouse embryonic stem cells; the encapsulated cells remained pluripotent in the absence of added LIF. These results illustrate a versatile strategy for the creation of information-rich biomaterials.

Item Type:Article
Related URLs:
URLURL TypeDescription Information CentralArticle
Mahdavi, Alborz0000-0002-8790-8112
Arnold, Frances H.0000-0002-4027-364X
Tirrell, David A.0000-0003-3175-4596
Additional Information:Copyright © 2014 National Academy of Sciences. Edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved July 1, 2014 (received for review January 21, 2014). Published ahead of print July 21, 2014. This research was funded by National Science Foundation Grant DMR 1206121 and by the Gordon and Betty Moore Foundation through Grant GBMF2809 to the California Institute of Technology Programmable Molecular Technology Initiative. F.S. and W.-B.Z. contributed equally to this work. Author contributions: F.S., W.-B.Z., F.H.A., and D.A.T. designed research; F.S., W.-B.Z., and A.M. performed research; F.S., W.-B.Z., and A.M. contributed new reagents/analytic tools; F.S., W.-B.Z., A.M., F.H.A., and D.A.T. analyzed data; and F.S., W.-B.Z., A.M., F.H.A., and D.A.T. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. This article contains supporting information online at
Funding AgencyGrant Number
Gordon and Betty Moore FoundationGBMF2809
Subject Keywords:protein biomaterials; stem cell encapsulation; cell fate control
Issue or Number:31
PubMed Central ID:PMC4128157
Record Number:CaltechAUTHORS:20140722-093927552
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Official Citation:Fei Sun, Wen-Bin Zhang, Alborz Mahdavi, Frances H. Arnold, and David A. Tirrell Synthesis of bioactive protein hydrogels by genetically encoded SpyTag-SpyCatcher chemistry PNAS 2014 111 (31) 11269-11274; published ahead of print July 21, 2014, doi:10.1073/pnas.1401291111
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:47388
Deposited By: George Porter
Deposited On:22 Jul 2014 19:56
Last Modified:10 Nov 2021 17:39

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