The strength of the protein-material interaction determines cell fate

Gonzalez Garcia, C., Cantini, M. , Ballester-Beltran, J., Altankov, G. and Salmeron-Sanchez, M. (2018) The strength of the protein-material interaction determines cell fate. Acta Biomaterialia, 77, pp. 74-84. (doi:10.1016/j.actbio.2018.07.016) (PMID:30006313)

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Abstract

Extracellular matrix (ECM) proteins are key mediators of cell/material interactions. The surface density and conformation of these proteins adsorbed on the material surface influence cell adhesion and the cellular response. We have previously shown that subtle variations in surface chemistry lead to drastic changes in the conformation of adsorbed fibronectin (FN). On poly(ethyl acrylate) (PEA), FN unfolds and displays domains for cell adhesion and FN-FN interaction, whereas on poly(methyl acrylate) (PMA) – with only one methyl group less – FN remains globular as it is in solution. The effect of the strength of the protein/material interaction in cell response, and its relation to protein density and conformation, has received limited attention so far. In this work, we used FN-functionalized AFM cantilevers to evaluate, via force spectroscopy, the strength of interaction between fibronectin and the underlying polymer which controls FN conformation (PEA and PMA). We found that the strength of FN/PEA interaction is significantly higher than FN/ PMA, which limits the mobility of FN layer on PEA, reduces the ability of cells to mechanically reorganize FN and then leads to enhanced proteolysis and degradation of the surrounding matrix with compromised cell viability. By contrast, both PEA and PMA support cell adhesion when FN density is increased and also in the presence of serum or other serum proteins, including vitronectin (VN) and bovine serum albumin (BSA), which provide a higher degree of mobility to the matrix.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and Cantini, Dr Marco and Gonzalez Garcia, Dr Cristina
Authors: Gonzalez Garcia, C., Cantini, M., Ballester-Beltran, J., Altankov, G., and Salmeron-Sanchez, M.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Acta Biomaterialia
Publisher:Elsevier
ISSN:1742-7061
ISSN (Online):1878-7568
Published Online:10 July 2018
Copyright Holders:Copyright © 2018 Acta Materialia Inc.
First Published:First published in Acta Biomaterialia 77: 74-84
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
722061Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - BIOMEDICAL ENGINEERING