Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro

Ashworth, J.C. et al. (2020) Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro. Matrix Biology, 85-86, pp. 15-33. (doi: 10.1016/j.matbio.2019.06.009) (PMID:31295578)

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Abstract

Current materials used for in vitro 3D cell culture are often limited by their poor similarity to human tissue, batch-to-batch variability and complexity of composition and manufacture. Here, we present a “blank slate” culture environment based on a self-assembling peptide gel free from matrix motifs. The gel can be customised by incorporating matrix components selected to match the target tissue, with independent control of mechanical properties. Therefore the matrix components are restricted to those specifically added, or those synthesised by encapsulated cells. The flexible 3D culture platform provides full control over biochemical and physical properties, allowing the impact of biochemical composition and tissue mechanics to be separately evaluated in vitro. Here, we demonstrate that the peptide gels support the growth of a range of cells including human induced pluripotent stem cells and human cancer cell lines. Furthermore, we present proof-of-concept the peptide gels can be used to build disease-relevant models. Controlling the peptide gelator concentration allows peptide gel stiffness to be matched to normal breast (<1 kPa) or breast tumour tissue (>1 kPa), with higher stiffness favouring the viability of breast cancer cells over normal breast cells. In parallel, the peptide gels may be modified with matrix components relevant to human breast, such as collagen I and hyaluronan. The choice and concentration of these additions affect the size, shape and organisation of breast epithelial cell structures formed in co-culture with fibroblasts. This system therefore provides a means of unravelling the individual influences of matrix, mechanical properties and cell-cell interactions in cancer and other diseases.

Item Type:Articles
Additional Information:The research described was funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) grant NC/N001583/1 (J.A., G.F., C.L.R.M.), and supported by the EPSRC/BBSRC/MRC (Engineering and Physical Sciences Research Council/Biotechnology and Biological Sciences Research Council/Medical Research Council) joint grants EP/R035067/1, EP/R035156/1 and EP/R035563/1 (M.T., A.J.W., C.L.R.M.), MRC grant MR/P003214/1 (K.P.A.), EPSRC/MRC CDT Regenerative Medicine and Faculty of Medical and Health Sciences (J.R.J., A.T., A.J.W., C.L.R.M.), EPSRC grant EP/N006615/1 (J.L.T., C.L.R.M.) and Swedish Research Council grant 2015-06532 (S.P.G.).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tassieri, Dr Manlio
Authors: Ashworth, J.C., Thompson, J.L., James, J.R., Slater, C.E., Pijuan-Galito, S., Lis-Slimak, K., Holley, R.J., Meade, K.A., Thompson, A., Arkill, K.P., Tassieri, M., Wright, A.J., Farnie, G., and Merry, C.L.R.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Matrix Biology
Publisher:Elsevier
ISSN:0945-053X
ISSN (Online):1569-1802
Published Online:08 July 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published Matrix Biology 85-86: 15-33
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
3014410Experiencing the micro-world - a cell's perspectiveManlio TassieriEngineering and Physical Sciences Research Council (EPSRC)EP/R035067/1ENG - Biomedical Engineering