Lingard, Eliana;
Dong, Siyuan;
Hoyle, Anna;
Appleton, Ellen;
Hales, Alis;
Skaria, Eldhose;
Lawless, Craig;
... Gilmore, Andrew P; + view all
(2024)
Optimising a self-assembling peptide hydrogel as a Matrigel alternative for 3-dimensional mammary epithelial cell culture.
Biomaterials Advances
, 160
, Article 213847. 10.1016/j.bioadv.2024.213847.
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Abstract
Three-dimensional (3D) organoid models have been instrumental in understanding molecular mechanisms responsible for many cellular processes and diseases. However, established organic biomaterial scaffolds used for 3D hydrogel cultures, such as Matrigel, are biochemically complex and display significant batch variability, limiting reproducibility in experiments. Recently, there has been significant progress in the development of synthetic hydrogels for in vitro cell culture that are reproducible, mechanically tuneable, and biocompatible. Self-assembling peptide hydrogels (SAPHs) are synthetic biomaterials that can be engineered to be compatible with 3D cell culture. Here we investigate the ability of PeptiGel® SAPHs to model the mammary epithelial cell (MEC) microenvironment in vitro. The positively charged PeptiGel®Alpha4 supported MEC viability, but did not promote formation of polarised acini. Modifying the stiffness of PeptiGel® Alpha4 stimulated changes in MEC viability and changes in protein expression associated with altered MEC function, but did not fully recapitulate the morphologies of MECs grown in Matrigel. To supply the appropriate biochemical signals for MEC organoids, we supplemented PeptiGels® with laminin. Laminin was found to require negatively charged PeptiGel® Alpha7 for functionality, but was then able to provide appropriate signals for correct MEC polarisation and expression of characteristic proteins. Thus, optimisation of SAPH composition and mechanics allows tuning to support tissue-specific organoids.
| Type: | Article |
|---|---|
| Title: | Optimising a self-assembling peptide hydrogel as a Matrigel alternative for 3-dimensional mammary epithelial cell culture |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.bioadv.2024.213847 |
| Publisher version: | https://doi.org/10.1016/j.bioadv.2024.213847 |
| Language: | English |
| Additional information: | © 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Hyrodgels, Breast epithelial cells, Breast cancer, Matrigel, Laminin, Mammary differentiation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > MAPS Faculty Office UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > MAPS Faculty Office > Institute for Materials Discovery |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10215736 |
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