Minor chemistry changes alter surface hydration to control fibronectin adsorption and assembly into nanofibrils

Bieniek, M., Llopis-Hernandez, V. , Douglas, K., Salmeron-Sanchez, M. and Lorenz, C. D. (2019) Minor chemistry changes alter surface hydration to control fibronectin adsorption and assembly into nanofibrils. Advanced Theory and Simulations, 2019(2), 1900169. (doi: 10.1002/adts.201900169)

198348.pdf - Published Version
Available under License Creative Commons Attribution.



Fibronectin (FN) is a large glycoprotein which links and transmits signals between the cell's cytoskeleton and the extracellular matrix. FN organization into fibrils and then fibrillogenesis can be induced with the right substrate, such as poly(ethyl acrylate) (PEA), on which FN becomes extended. Interestingly, the almost identical polymer poly(methyl acrylate) (PMA), which has one less methylene bridge (─CH2─), does not cause fibrillogenesis. To investigate the difference in FN behavior on PEA and PMA, the two substrates are modeled using ethyl acrylate (EA) and methyl acrylate (MA) functionalized self‐assembled monolayers (SAMs). It is confirmed experimentally that the EA and MA SAMs exhibit a similar behavior in vitro to the polymers in terms of fibronectin fibrillogenesis, domain exposure, and cell adhesion. All‐atom molecular dynamics simulations of the FNIII 9‐10 domains interacting with each SAM show the adsorption of these two domains on EA SAMs and no adsorption on MA SAMs. Consistently, the experiments show that FN fibrillogenesis takes place on EA SAMs but not on MA SAMs. It is found that the extra methylene group in the EA headgroup leads to more motion within the headgroup that results in a markedly less dense hydration layer, which facilitates FN fibrillogenesis.

Item Type:Articles
Additional Information:M.K.B. and C.D.L. acknowledge the support by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001179), the UK Medical Research Council (FC001179), and the Wellcome Trust (FC001179). Additionally, M.K.B. acknowledges the valuable conversations he had with Willie Taylor and Enrico Spiga at the Francis Crick Institute during the course of this study. Via the authors’ membership of the UK’s HEC Materials Chemistry Consortium, which is funded by EPSRC (EP/L000202/1, EP/R029431/1), this work used the ARCHER UK National Supercomputing Service (http://www.archer.ac.uk) and the UK Materials and Molecular Modelling Hub (MMM Hub) for computational resources, which is partially funded by EPSRC (EP/P020194/1) to carry out theMDsimulations reported in thismanuscript. This study was supported by the UK Regenerative Medicine Platform (MRC Grant MR/L022710/1) and the UK Engineering and Physical Sciences Research Council (EPSRC EP/P001114/1). X-ray photoelectron spectroscopy was conducted by the National EPSRC XPS Users’ Service (NEXUS), Newcastle.
Glasgow Author(s) Enlighten ID:Douglas, Miss Katie and Salmeron-Sanchez, Professor Manuel and Llopis-Hernandez, Dr Virginia
Authors: Bieniek, M., Llopis-Hernandez, V., Douglas, K., Salmeron-Sanchez, M., and Lorenz, C. D.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
College of Science and Engineering > School of Engineering
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Advanced Theory and Simulations
ISSN (Online):2513-0390
Published Online:28 October 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Advanced Theory and Simulations 2019(2):1900169
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173192Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - Biomedical Engineering