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Nat Mater. 2019 May 20. doi: 10.1038/s41563-019-0367-7. [Epub ahead of print]

Bioactive site-specifically modified proteins for 4D patterning of gel biomaterials.

Author information

1
Department of Chemical Engineering, University of Washington, Seattle, WA, USA.
2
Department of Biochemistry, University of Washington, Seattle, WA, USA.
3
Department of Chemical Engineering, University of Washington, Seattle, WA, USA. profcole@uw.edu.
4
Department of Bioengineering, University of Washington, Seattle, WA, USA. profcole@uw.edu.
5
Institute for Stem Cell & Regenerative Medicine, University of Washington, Seattle, WA, USA. profcole@uw.edu.
6
Molecular Engineering & Sciences Institute, University of Washington, Seattle, WA, USA. profcole@uw.edu.

Abstract

Protein-modified biomaterials can be used to modulate cellular function in three dimensions. However, as the dynamic heterogeneous control over complex cell physiology continues to be sought, strategies that permit a 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 homogeneous, 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. Localized epidermal growth factor presentation enables dynamic regulation over proliferation, intracellular mitogen-activated protein kinase signalling and subcellularly resolved receptor endocytosis. Our method broadly permits the modification and patterning of a wide range of proteins, which provides newfound avenues to probe and direct advanced cellular fates in four dimensions.

PMID:
31110347
DOI:
10.1038/s41563-019-0367-7

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