Tailoring Collagen to Engineer the Cellular Microenvironment.

Autor: Que RA; Department of Biomedical Engineering, University of California, Irvine, CA, 92697, USA., Crakes DR; Department of Biomedical Engineering, University of California, Irvine, CA, 92697, USA., Abdulhadi F; Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA., Niu CH; Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA., Da Silva NA; Department of Biomedical Engineering, University of California, Irvine, CA, 92697, USA.; Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA., Wang SW; Department of Biomedical Engineering, University of California, Irvine, CA, 92697, USA.; Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA.
Jazyk: angličtina
Zdroj: Biotechnology journal [Biotechnol J] 2018 Dec; Vol. 13 (12), pp. e1800140. Date of Electronic Publication: 2018 Sep 21.
DOI: 10.1002/biot.201800140
Abstrakt: Collagen is the most abundant protein in the extracellular matrix (ECM), and it can direct the behavior of the neighboring cells. By customizing properties of collagen, it is possible to control the cells that interact with it. Utilizing a bottom-up strategy, modular gene fragments are assembled and recombinantly processed to create collagen-mimetic variants that modulate proteolytic degradation, cell adhesion, and mechanical characteristics. The removal of the native MMP cleavage site results in MMP-1 resistant collagen. By introducing additional MMP-susceptible sequences, the degradation characteristics of collagen molecules are modified. Additional non-native functionality is also introduced into the collagen, including the IKVAV sequence, which has been implicated in neurite outgrowth. This mutation, which disrupts the Gly-X-Y tripeptide repeat of collagen, does not prevent the formation of triple-helical collagen. Non-native cysteines and the integrin binding sequence GFOGER are combined in the collagen, and encapsulation of normal human lung fibroblasts within collagen hydrogels are tested. Cells remain spherical, when encapsulated within hydrogels of collagen variants in which the native integrin binding sites are removed, but cell adhesion is restored with the introduction of non-native GFOGER binding sequences. This modular collagen system allows for the combination of multiple functionalities, and it enables the production of biomimetic scaffolds with customizable characteristics to modulate cellular microenvironments.
(© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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