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Bioactive Site-Specifically Modified Proteins for 4D Patterning of Gel Biomaterials

Protein-modified biomaterials can be used to modulate cellular function in 3D. However, as dynamic heterogeneous control over complex cell physiology continues to be sought, strategies that permit reversible and user-defined tethering of fragile proteins to materials remain in great need. Here, we i...

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Detalles Bibliográficos
Autores principales: Shadish, Jared A., Benuska, Gabrielle M., DeForest, Cole A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706293/
https://www.ncbi.nlm.nih.gov/pubmed/31110347
http://dx.doi.org/10.1038/s41563-019-0367-7
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author Shadish, Jared A.
Benuska, Gabrielle M.
DeForest, Cole A.
author_facet Shadish, Jared A.
Benuska, Gabrielle M.
DeForest, Cole A.
author_sort Shadish, Jared A.
collection PubMed
description Protein-modified biomaterials can be used to modulate cellular function in 3D. However, as dynamic heterogeneous control over complex cell physiology continues to be sought, strategies that permit reversible and user-defined tethering of fragile proteins to materials remain in great need. Here, we introduce a modular and robust semisynthetic approach to reversibly pattern cell-laden hydrogels with site-specifically modified proteins. Exploiting a versatile sortase-mediated transpeptidation, we generate a diverse library of homogenous, singly functionalized proteins with bioorthogonal reactive handles for biomaterial modification. We demonstrate the photoreversible immobilization of fluorescent proteins, enzymes, and growth factors to gels with excellent spatiotemporal resolution while retaining native protein bioactivity. Dynamic regulation of proliferation, intracellular mitogen-activated protein kinase signaling, and subcellularly resolved receptor endocytosis is accomplished through localized epidermal growth factor presentation. Our method broadly permits modification and patterning of a wide range of proteins, providing newfound avenues to probe and direct advanced cellular fates in 4D.
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spelling pubmed-67062932019-11-20 Bioactive Site-Specifically Modified Proteins for 4D Patterning of Gel Biomaterials Shadish, Jared A. Benuska, Gabrielle M. DeForest, Cole A. Nat Mater Article Protein-modified biomaterials can be used to modulate cellular function in 3D. However, as dynamic heterogeneous control over complex cell physiology continues to be sought, strategies that permit reversible and user-defined tethering of fragile proteins to materials remain in great need. Here, we introduce a modular and robust semisynthetic approach to reversibly pattern cell-laden hydrogels with site-specifically modified proteins. Exploiting a versatile sortase-mediated transpeptidation, we generate a diverse library of homogenous, singly functionalized proteins with bioorthogonal reactive handles for biomaterial modification. We demonstrate the photoreversible immobilization of fluorescent proteins, enzymes, and growth factors to gels with excellent spatiotemporal resolution while retaining native protein bioactivity. Dynamic regulation of proliferation, intracellular mitogen-activated protein kinase signaling, and subcellularly resolved receptor endocytosis is accomplished through localized epidermal growth factor presentation. Our method broadly permits modification and patterning of a wide range of proteins, providing newfound avenues to probe and direct advanced cellular fates in 4D. 2019-05-20 2019-09 /pmc/articles/PMC6706293/ /pubmed/31110347 http://dx.doi.org/10.1038/s41563-019-0367-7 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Shadish, Jared A.
Benuska, Gabrielle M.
DeForest, Cole A.
Bioactive Site-Specifically Modified Proteins for 4D Patterning of Gel Biomaterials
title Bioactive Site-Specifically Modified Proteins for 4D Patterning of Gel Biomaterials
title_full Bioactive Site-Specifically Modified Proteins for 4D Patterning of Gel Biomaterials
title_fullStr Bioactive Site-Specifically Modified Proteins for 4D Patterning of Gel Biomaterials
title_full_unstemmed Bioactive Site-Specifically Modified Proteins for 4D Patterning of Gel Biomaterials
title_short Bioactive Site-Specifically Modified Proteins for 4D Patterning of Gel Biomaterials
title_sort bioactive site-specifically modified proteins for 4d patterning of gel biomaterials
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706293/
https://www.ncbi.nlm.nih.gov/pubmed/31110347
http://dx.doi.org/10.1038/s41563-019-0367-7
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