Fibronectin-matrix sandwich-like microenvironments to manipulate cell fate

Ballester-Beltrán, J., Moratal, D., Lebourg, M. and Salmeron-Sanchez, M. (2014) Fibronectin-matrix sandwich-like microenvironments to manipulate cell fate. Biomaterials Science, 2(3), pp. 381-389. (doi:10.1039/C3BM60248F)

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Conventional 2D substrates fail to represent the natural environment of cells surrounded by the 3D extracellular matrix (ECM). We have proposed sandwich-like microenvironments as a versatile tool to study cell behaviour under quasi-3D conditions. This is a system that provides a broad range of dorsal and ventral independent spatio-temporal stimuli. Here, we use this sandwich technology to address the role of dorsal stimuli in cell adhesion, cell proliferation and ECM reorganisation. Under certain conditions, dorsal stimuli within sandwich microenvironments prevent the formation of focal plaques as well as the development of the actin cytoskeleton, whereas α5versus αv integrin expression is increased compared to the corresponding 2D controls. Cell signaling is similarly enhanced after dorsal stimuli (measured by the pFAK/FAK level) for cells sandwiched after 3 h of 2D ventral adhesion, but not when sandwiched immediately after cell seeding (similar levels to the 2D control). Cell proliferation, studied by the 5-bromo-2-deoxyuridine (BrdU) incorporation assay, was significantly reduced within sandwich conditions as compared to 2D substrates. In addition, these results were found to depend on the ability of cells to reorganise the dorsal layer of proteins at the material interface, which could be tuned by adsorbing FN on material surfaces that results in a qualitatively different conformation and distribution of FN. Overall, sandwich-like microenvironments switch cell behaviour (cell adhesion, morphology and proliferation) towards 3D-like patterns, demonstrating the importance of this versatile, simple and robust approach to mimic cell microenvironments in vivo.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel
Authors: Ballester-Beltrán, J., Moratal, D., Lebourg, M., and Salmeron-Sanchez, M.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Biomaterials Science
Publisher:R S C Publications
ISSN (Online):2047-4849
Copyright Holders:Copyright © 2014 The Royal Society of Chemistry
First Published:First published in Biomaterials Science 2(3):381-389
Publisher Policy:Reproduced under a Creative Commons License

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