Self-Assembling Polypeptide Hydrogels as a Platform to Recapitulate the Tumor Microenvironment
Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, South Kensington Campus, Imperial College London, London SW7 2AZ, UK
Department of Materials, Manchester Institute of Biotechnology, Faculty of Science and Engineering, The University of Manchester, Oxford Road, Manchester M13 9PL, UK
Department of Chemical Engineering and Analytical Science, Manchester Institute of Biotechnology, Faculty of Science and Engineering, The University of Manchester, Oxford Road, Manchester M13 9PL, UK
Manchester BIOGEL, Mereside, Alderley Park, Alderley Edge, Cheshire SK10 4TG, UK
Authors to whom correspondence should be addressed.
Academic Editor: Olivier Feron
Received: 5 June 2021
Revised: 22 June 2021
Accepted: 25 June 2021
Published: 30 June 2021
The tumor microenvironment is characterized by increased tissue stiffness, low (acidic) pH, and elevated temperature, all of which contribute to the development of cancer. Improving our in vitro models of cancer, therefore, requires the development of cell culture platforms that can mimic these microenvironmental properties. Here, we study a new biomaterial composed of short amino acid chains that self-assemble into a fibrous hydrogel network. This material enables simultaneous and independent tuning of substrate rigidity, extracellular pH, and temperature, allowing us to mimic both healthy tissues and the tumor microenvironment. We used this platform to study the effect of these conditions on pancreatic cancer cells and found that high substrate rigidity and low pH promote proliferation and survival of cancer cells and activate important signaling pathways associated with cancer progression.